ovalbumin and Anaphylaxis

CME EDUCATIONAL OBJECTIVES 1. Understand that trivalent influenza vaccine is safe for patients with egg allergy, including patients with severe egg allergy. 2. Understand that egg-allergic patients no longer require any special precautions to safely receive trivalent influenza vaccine. 3. Recognize that the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices advises that most egg-allergic patients can now receive trivalent influenza vaccine from their primary care physician. Trivalent influenza vaccine is grown in chick embryos and contains residual egg protein (ovalbumin). Historically, trivalent influenza vaccine (TIV) has been contraindicated in egg-allergic individuals (EAI) and the vaccine was withheld in many of these individuals due to the ovalbumin. However, protocols were developed that allowed EAIs to safely receive TIV, including stepwise desensitization, vaccine skin testing, and use of low ovalbumin containing vaccine. In the past 3 years, several groups have systematically disproven that EAI are at any increased risk for an allergic reaction than the general population and withholding TIV is not necessary. To date, approximately 4,315 patients have safely received 4,872 total doses of TIV, including 656 EAI with severe egg allergy (including anaphylaxis to egg) who safely received 740 doses of TIV. Thus, it is as safe to provide TIV to EAI as providing it to a non-EAI. This article will trace the evolution of this practice.

Topics: Anaphylaxis; Dose-Response Relationship, Drug; Egg Hypersensitivity; Humans; Influenza A Virus, H1N1 Subtype; Influenza Vaccines; Ovalbumin; Patient Safety; Risk Assessment; Severity of Illness Index; Skin Tests; Vaccination

Topics: Allergens; Anaphylaxis; Canada; Egg Hypersensitivity; Humans; Influenza Vaccines; Influenza, Human; Ovalbumin; Prospective Studies; Risk

The cytosolic 85 kDa phospholipase A(2) (cPLA(2)) is a unique member of the phospholipase A(2) (PLA(2)) superfamily. Because PLA(2) activity and eicosanoid production are important in normal and pathophysiological states we and the laboratory of Shimizu created a mouse deficient in cPLA(2) (cPLA(2)(-/-) mouse). cPLA(2)(-/-) mice develop normally but the females have severe reproductive defects. cPLA(2)(-/-) mice suffer smaller infarcts and fewer neurological deficits after transient occlusion of the middle cerebral artery and have less injury after administration of a dopaminergic selective neurotoxin. cPLA(2)(-/-) mice have a more rapid recovery from allergen-induced bronchoconstriction and have no airway hyperresponsiveness. Peritoneal macrophages from cPLA(2)(-/-) mice fail to produce prostaglandins, leukotriene B(4) and cysteinyl leukotrienes after stimulation. Bone marrow-derived mast cells from cPLA(2)(-/-) mice fail to produce eicosanoids in either immediate or delayed phase responses. Thus the cPLA(2) knockout mouse has revealed important roles of cPLA(2) in normal fertility, generation of eicosanoids from inflammatory cells, brain injuries and allergic responses. Furthermore the cPLA(2)(-/-) mouse reveals that the many other forms of PLA(2) cannot replace many functions of cPLA(2). The importance of cPLA(2) in inflammation and tissue injury suggests that pharmacological targeting of this enzyme may have important therapeutic benefits.

Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Airway Resistance; Anaphylaxis; Animals; Brain Injuries; Brain Ischemia; Bronchoconstriction; Cytosol; Female; Gene Deletion; Leukotriene B4; Leukotriene C4; Lipopolysaccharides; Litter Size; Macrophages, Peritoneal; Methacholine Chloride; Mice; Mice, Inbred C57BL; Mice, Knockout; Middle Cerebral Artery; Models, Animal; Ovalbumin; Phospholipases A; Pregnancy

IgE-mediated histamine release was studied using the method of passive peritoneal anaphylaxis (PPA) in the rat. Some beta-adrenergic stimulants markedly inhibited this reaction in vivo, the order of potency (ED50 microng/kg i.v.) of agents tested being fenoterol (6), salbutamol (40) and isoproterenol (94). Higher activity against the simultaneously measured dye extravasation suggested a dual effect of the drugs on both the cellular (inhibition of histamine release) and the vascular level. The order of potency in modifying vascular injury was, however, reversed, isoproterenol and not fenoterol being relatively more active here, as could be shown by further experiments. Inhibition of histamine release is discussed with respect to (a) methodical requirements and (b) the suggestion that beta2-receptor stimulants (fenoterol, salbutamol) are more selective than isoproterenol.

Topics: Adrenergic beta-Agonists; Anaphylaxis; Animals; Antigens; Ascitic Fluid; Cromolyn Sodium; Dextrans; Dose-Response Relationship, Drug; Edema; Evans Blue; Fenoterol; Histamine Release; Immunoglobulin E; Male; Ovalbumin; Rats; Serotonin

Topics: Adrenal Glands; Anaphylaxis; Animals; Antigen-Antibody Reactions; Carbohydrates; Egg White; Fibrinolysin; Globulins; Histamine; Hormones; Humans; Hypersensitivity; Kinins; Mast Cells; Muramidase; Neuraminic Acids; Ovalbumin; Pancreas; Rats; Serotonin; Thyroid Gland

Topics: Anaphylaxis; Child, Preschool; Egg Hypersensitivity; Humans; Infant; Influenza Vaccines; Ovalbumin; Prospective Studies; Retrospective Studies; Skin Tests

Recent Australian and international legislation requires labeling of wines made by using the potentially allergenic food proteins casein, milk, egg white, or isinglass (fish-derived) where "there is a detectable residual processing aid." We investigated whether wines fined using these proteins or non-grape-derived tannins (tree-nut derived) can provoke significant clinical allergic reactions (anaphylaxis) in patients with confirmed immunoglobulin E-mediated relevant food allergy.. A double-blind, placebo-controlled trial was performed to determine whether allergic reactions followed consumption of Australian commercial wines fined using one or more of the legislation-targeted food proteins. In addition, allergenicity of a larger panel of these wines was evaluated by blood basophil activation.. No anaphylaxis was induced by wine consumption. Three mild clinical reactions to protein-fined wine and two mild reactions to unfined wine occurred, but there was no statistically significant difference in reaction parameters between subject groups or between processing aids. No pattern of basophil activation correlated with wine type, processing aid, or subject group.. Wines fined with egg white, isinglass, or non-grape-derived tannins present an extremely low risk of anaphylaxis to fish-, egg-, or peanut-allergic consumers. Although consumption of milk protein-fined wine did not induce anaphylaxis, there were insufficient subjects to determine statistically whether wines fined with milk proteins present a risk to the very rare milk-allergic consumers. In summary, the observed lack of anaphylaxis and basophil activation induced by wines made using the legislation-targeted food proteins according to good manufacturing practice suggests negligible residual food allergens in these wines.

Topics: Adult; Allergens; Anaphylaxis; Arachis; Basophils; Caseins; Double-Blind Method; Female; Food Contamination; Food Handling; Food Hypersensitivity; Gelatin; Humans; Male; Middle Aged; Ovalbumin; Tannins; Wine; Young Adult

Topics: Allergens; Anaphylaxis; Animals; Asthma; Bronchi; Bronchial Provocation Tests; Chromones; Drug Evaluation; Drug Evaluation, Preclinical; Dust; Guinea Pigs; Histamine; Humans; Immunization, Passive; Indomethacin; Male; Ovalbumin; Pyrilamine; SRS-A

Allergy is mediated by the crosslinking of immunoglobulins (Ig) -E or -G to their respective receptors, which degranulates mast cells, macrophages, basophils, or neutrophils, releasing allergy-causing mediators. The removal of these mediators such as histamine, platelet-activating factor (PAF) and interleukins (ILs) released by effector cells will alleviate allergy. Clinacanthus nutans (C. nutans), an herbal plant in Southeast Asia, is used traditionally to treat skin rash, an allergic symptom. Previously, we have reported that C. nutans aqueous leaves extract (CNAE) was able to suppress the release of β-hexosaminidase and histamine but not interleukin-4 (IL-4) and tumor necrosis factor-alpha (TNF-α) in the IgE-induced mast cell degranulation model at 5 mg/mL and above. We also found that CNAE could protect rats against ovalbumin-challenged active systemic anaphylaxis (OVA-ASA) through the downregulation and upregulation of certain metabolites using proton nuclear magnetic resonance (. As allergy could be mediated by both IgE and IgG, we further evaluated the anti-allergy potential of CNAE in both in vitro model of IgG-induced macrophage activation and in vivo anaphylaxis models to further dissect the mechanism of action underlying the anti-allergic properties of CNAE.. The anti-allergy potential of CNAE was evaluated in in vivo anaphylaxis models of ovalbumin-challenged active systemic anaphylaxis (OVA-ASA) and IgE-challenged passive systemic anaphylaxis (PSA) using Sprague Dawley rats as well as IgG-challenged passive systemic anaphylaxis (IgG-PSA) using C57BL/6 mice. Meanwhile, in vitro model of IgG-induced macrophage activation model was performed using IC-21 macrophages. The release of soluble mediators from both IgE and IgG-mediated pathways were measured using enzyme-linked immunosorbent assay (ELISA). The signaling molecules targeted by CNAE were identified by performing Western blot.. Overall, our findings supported that CNAE exerts its anti-allergic properties by suppressing the IgG pathway and its mediators by inhibiting ERK1/2 phosphorylation, thus providing scientific evidence supporting its traditional use in managing allergy.

Topics: Anaphylaxis; Animals; Anti-Allergic Agents; Histamine; Immunoglobulin E; Immunoglobulin G; Interleukin-4; Interleukin-6; Mast Cells; Mice; Mice, Inbred C57BL; Ovalbumin; Platelet Activating Factor; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha

Food allergies (FAs) are caused by a failure of the immune system to regulate oral tolerance (OT). The use of soap containing hydrolyzed wheat overrides acquired OT to wheat through skin exposure. However, in mouse models, the experimental OT is robust, suggesting that acquired OT to allergens prevents the development of FAs. We aimed to analyze the mechanisms and developed a mouse model of FA that overrides acquired OT via skin exposure. Three murine FA models (intraperitoneal [IP], epicutaneous [EC], and intradermal [ID]) were compared to evaluate if allergies to ovalbumin (OVA) that had been previously tolerated orally could be induced. In the ID model, OT was overridden, and allergic reactions of severe anaphylaxis were developed. To analyze this effect in the ID model, we measured the migration of dendritic cells (DCs) into lymph nodes. The induction of OT promoted the migration of CD103

Topics: Allergens; Anaphylaxis; Animals; Disease Models, Animal; Food Hypersensitivity; Mice; Mice, Inbred BALB C; Ovalbumin; Skin

Topics: Anaphylaxis; Animals; Anti-Allergic Agents; Mast Cells; Mice; MTOR Inhibitors; Ovalbumin; Phosphatidylinositol 3-Kinases; TOR Serine-Threonine Kinases

The risk of developing anaphylactic reactions to medications introduces additional difficulties for effective pharmacotherapy. Using a model of systemic anaphylaxis in mice, we showed that preventive administration of a preparation containing technologically processed antibodies (TPA) to MHC II induces an anti-anaphylactic effect comparable to that of dexamethasone (when assessing the severity of systemic anaphylaxis 30 and 60 min after challenge injection of the model antigen ovalbumin). The revealed activity may be related to the ability of TPA to MHC II to regulate the antigen presentation system and shift the immune response towards the production of IgG instead of IgE typical of anaphylactic reaction.

Topics: Anaphylaxis; Animals; Anti-Allergic Agents; Antibodies; Mice; Ovalbumin

Anemoside B4 (AB4) is a natural triterpenoid abundant in the roots of Pulsatilla chinensis. Although various biological activities have been widely attributed to AB4, few studies have focused on its antiallergic effects. In this study the inhibitory effects of AB4 on immunoglobulin E (IgE)-mediated allergic responses were investigated, both in vitro and in vivo, and the mechanism of its effects. IgE-mediated passive cutaneous anaphylaxis was used to elucidate the antiallergic effects of AB4 in vivo. The degranulation assay, calcium imaging, and cytokine and chemokine release in the laboratory of allergic disease 2 (LAD2) cell line were used to evaluate the antiallergic effect of AB4 in vitro. Pathological staining was performed to analyze angiectasis. Western blot analysis was performed to investigate the downstream signaling pathways. AB4 dose-dependently attenuated ovalbumin/IgE-induced paw swelling in mice, and reduced the serum concentrations of tumor necrosis factor-alpha and C-C motif chemokine 2. In addition, AB4 suppressed IgE-mediated LAD2 cell degranulation, calcium influx, and PLC/IP3 and JAK/STAT3 phosphorylation. Our results suggest that AB4 inhibits allergic reactions through the PLC/IP3 and JAK/STAT3 pathways.

Topics: Anaphylaxis; Animals; Anti-Allergic Agents; Calcium; Cell Degranulation; Congenital Disorders of Glycosylation; Cytokines; Hypersensitivity; Immunoglobulin E; Mast Cells; Mice; Ovalbumin; Passive Cutaneous Anaphylaxis; Saponins; Triterpenes; Tumor Necrosis Factor-alpha

Food allergy is an antigen-specific immunological adverse reaction after exposure to a given food. Multiple clinical studies showed that oral immunotherapy (OIT) is effective for the prevention and treatment for food allergy that is developed in infants and children. However, the effectiveness of OIT for epicutaneously sensitized food allergy remains unclear. Previously, we established a mouse model of epicutaneous-sensitized food allergy. In this model, systemic allergic reaction including intestinal and skin symptoms, such as anaphylaxis, was observed. We treated this model with OIT in two ways (OIT before sensitization or OIT during the sensitization phase) and evaluated the preventive effect of both methods. OIT before sensitization significantly ameliorated mast cell degranulation in sensitized skin, but there was no decrease in rectal temperatures or in mast cell degranulation in the jejunum. However, OIT administered during the sensitization phase significantly ameliorated the decrease in rectal temperature and mast cell degranulation in the skin and jejunum. OIT before sensitization increased the regulatory T cells in mesenteric lymph node (MLN), but not in the spleen, and it reduced antigen-specific IgG, but not IgE, production compared with the non-OIT control. However, OIT during sensitization caused a greater increase in regulatory T cells in both the MLN and spleen and reduced antigen-specific IgE and IgG generation compared with the non-OIT control group. Thus, OIT during the sensitization phase was effective for the prevention of epicutaneous-sensitized food allergy.

Topics: Administration, Cutaneous; Administration, Oral; Anaphylaxis; Animals; Antigens; Body Temperature; Cell Degranulation; Chymases; Desensitization, Immunologic; Disease Models, Animal; Food Hypersensitivity; Immune Tolerance; Immunoglobulin E; Immunoglobulin G; Jejunum; Lymph Nodes; Mast Cells; Mesentery; Mice; Ovalbumin; Skin; Skin Diseases; Spleen; T-Lymphocytes, Regulatory

The targeting of natural tolerogenic liver sinusoidal endothelial cells (LSEC) by nanoparticles (NPs), decorated with a stabilin receptor ligand, is capable of generating regulatory T-cells (Tregs), which can suppress antigen-specific immune responses, including to ovalbumin (OVA), a possible food allergen. In this regard, we have previously demonstrated that OVA-encapsulating poly(lactic-

Topics: Anaphylaxis; Animals; Cytokines; Endothelial Cells; Epitopes; Liver; Mice; Mice, Inbred BALB C; Nanoparticles; Ovalbumin; Pharmaceutical Preparations

We previously described that Porphyra haitanensis sulfated polysaccharide (PHSP) maintains the balance of pro-inflammation and immunosuppression. However, it is unclear whether degraded PHSP (DPHSP) still shows the immunomodulatory activity. Here, we degraded PHSP by four different methods alone or combined in pairs, and the results showed that the molecular weight and viscosity of DPHSP were significantly decreased, while the main chemical bonds and functional structure were consistent with those of PHSP. We then investigated the immunomodulatory function of DPHSP in vitro and in vivo. Actually, DPHSP enhances the inhibitory effects on mast cell activation and improves the suppression activity of PHSP on the food anaphylactic response. In an ovalbumin-induced food allergy mouse model, the production of allergic mediators and cytokines (interleukin-4 and 13, and interferon-γ) was inhibited by DPHSP. Meanwhile, DPHSP had a stronger ability to up-regulate the differentiation of regulatory T (Treg) cells and its related cytokines. These results suggested that DPHSP showed a better anti-food allergic ability than PHSP by regulating T helper cell balance and promoting Treg cell differentiation, which indicates that DPHSP is a novel potential nutrient component against food allergy.

Topics: Anaphylaxis; Animals; Anti-Allergic Agents; Antibodies; Cell Differentiation; Cytokines; Female; Food Hypersensitivity; Histamine; Mice; Mice, Inbred BALB C; Ovalbumin; Polysaccharides; Porphyra; Sulfates; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory

Anaphylaxis represents one of the most severe and fatal forms of allergic reactions. Like most other allergies, it is caused by activation of basophils and mast cells by allergen-mediated cross-linking of IgE bound to its high-affinity receptor, FcεRI, on the cell surface. The systemic release of soluble mediators induces an inflammatory cascade, rapidly causing symptoms with peak severity in minutes to hours after allergen exposure. Primary treatment for anaphylaxis consists of immediate intramuscular administration of adrenaline.. While adrenaline alleviates life-threatening symptoms of an anaphylactic reaction, there are currently no disease-modifying interventions available. We sought to develop potent and fast-acting IgE inhibitors with the potential to rapidly terminate acute allergic reactions.. Using affinity maturation by yeast display and structure-guided molecular engineering, we generated 3 optimized disruptive IgE inhibitors based on designed ankyrin repeat proteins and assessed their ability to actively remove IgE from allergic effector cells in vitro as well as in vivo in mice.. The engineered IgE inhibitors rapidly dissociate preformed IgE:FcεRI complexes, terminate IgE-mediated signaling in preactivated human blood basophils in vitro, and shut down preinitiated allergic reactions and anaphylaxis in mice in vivo.. Fast-acting disruptive IgE inhibitors demonstrate the feasibility of developing kinetically optimized inhibitors for the treatment of anaphylaxis and the rapid desensitization of allergic individuals.

Topics: Allergens; Anaphylaxis; Animals; Basophils; Drug Design; Humans; Immunoglobulin E; Mice, Transgenic; Molecular Structure; Ovalbumin; Receptors, IgE; Recombinant Fusion Proteins

Topics: Anaphylaxis; Animals; Body Fluids; Brain Chemistry; Cell Degranulation; Cell Hypoxia; Chymases; Cold Temperature; Female; Hypothermia; Kidney; Mast Cells; Mice; Mice, Inbred C57BL; NAD; Ovalbumin; Oxygen

To better explore the pathophysiology of FA and its therapy, we aimed to establish a simple and practicable FA model with Freund's adjuvant and introduce an easy and reliable laboratory evaluation method for assessment of inflammation in intestinal segments at different anatomical locations. BALB/c mice were sensitized with ovalbumin combined with Freund's adjuvant. Complete Freund's adjuvant was chosen for the first sensitization and two weeks later incomplete Freund's adjuvant was used for a second sensitization. Two weeks later, the sensitized mice were challenged with 50 mg ovalbumin every other day. After the 6 challenge, all mice were assessed for systemic anaphylaxis, and then sacrificed for sample collection. All sensitized mice showed anaphylactic symptoms and markedly increased levels of serum ovalbumin-specific IgE and IgG1. The activity of mast cell protease-1 (mMCPT-1) was significantly increased in the serum and interstitial fluid of the duodenum, jejunum, ileum, and colon. A successful FA model was established, of which inflammation occurred in the duodenum, jejunum, ileum, and colon. This model provides a reliable and simple tool for analysis of the mechanism of FA and methods of immunotherapy. Moreover, combined detection of ovalbumin-specific antibody and local mMCPT-1 levels could potentially be used as the major indicator for assessment of food allergy.

Topics: Anaphylaxis; Animals; Biomarkers; Chymases; Colon; Duodenum; Egg Hypersensitivity; Extracellular Fluid; Female; Freund's Adjuvant; Gene Expression; Ileum; Immunoglobulin E; Immunoglobulin G; Jejunum; Mice; Mice, Inbred BALB C; Ovalbumin

A promising approach to treat a variety of diseases are considered as complementary and alternative herbal medicines. Prunus serrulata var. spontanea L. (Rosaceae) is used as herbal medicine to treat allergic diseases according to the Donguibogam, a tradition medical book of the Joseon Dynasty in Korea.. We prepared the aqueous extract of the bark of P. serrulata (AEBPS) and aimed to investigate the effects in mouse anaphylaxis models and various types of mast cells, including RBL-2H3, primary cultured peritoneal and bone marrow-derived mast cells.. We used ovalbumin (OVA)-induced active systemic anaphylaxis (ASA) and immunoglobulin (Ig) E-mediated passive cutaneous anaphylaxis (PCA) models, in vivo. The control drug dexamethasone (10 mg/kg) was used to compare the effectiveness of AEBPS (1-100 mg/kg). In vitro, IgE-stimulated mast cells were used to confirm the role of AEBPS (1-100 μg/mL). For statistical analyses, p values less than 0.05 were considered to be significant.. In ASA model, oral administration of AEBPS suppressed the hypothermia and increased level of serum histamine in a dose-dependent manner. AEBPS attenuated the serum IgE, OVA-specific IgE, and interleukin (IL)-4. Oral administration of AEBPS also blocked mast cell-dependent PCA. AEBPS suppressed degranulation of mast cells by reducing intracellular calcium level in mast cells. AEBPS inhibited tumor necrosis factor-α and IL-4 expression and secretion in a concentration-dependent manner through the reduction of nuclear factor-κB.. On the basis of these findings, AEBPS could serve as a potential therapeutic target for the management of mast cell-mediated allergic inflammation and as a regulator of mast cell activation.

Topics: Anaphylaxis; Animals; Dose-Response Relationship, Drug; Histamine; Immunoglobulin E; Male; Mast Cells; Medicine, Korean Traditional; Mice; Mice, Inbred ICR; Ovalbumin; Passive Cutaneous Anaphylaxis; Plant Bark; Plant Extracts; Prunus; Rats; Rats, Sprague-Dawley

A previous study revealed that fucoidan inhibited mast cell degranulation through the upregulation of galectin-9 in blood. The purpose of this study is to elucidate its mechanism using ovalbumin (OVA) induced anaphylaxis model mice (BALB/c, Female, 5-week-old) and mast cell line (RBL-2H3 cells). Oral administration of fucoidan after sensitization with OVA/Al(OH)

Topics: Administration, Oral; Allergens; Anaphylaxis; Animals; Anti-Allergic Agents; Bodily Secretions; Cell Line; Epithelial Cells; Female; Galectins; Humans; Mast Cells; Mice; Mice, Inbred BALB C; Ovalbumin; Plant Extracts; Polysaccharides; Rats

Topics: Anaphylaxis; Animals; Anti-Inflammatory Agents; Calcium; Calcium Signaling; Cell Degranulation; Cell Survival; Cells, Cultured; Gallic Acid; Immunoglobulin E; Inflammation; Male; Mast Cells; Mice; Mice, Inbred ICR; Ovalbumin; Passive Cutaneous Anaphylaxis; Rats; Rats, Sprague-Dawley; Receptors, IgE

Glycomacropeptide (GMP) is a bioactive peptide derived from milk κ-casein with immune-modulatory and anti-inflammatory properties. Food allergy (FA) is an adverse immune reaction with a broad spectrum of manifestations. Allergen intake induces persistent intestinal inflammation and tissue damage. In this study, the anti-allergic activity of GMP was evaluated using a rat ovalbumin (OVA)-induced FA model with gastrointestinal manifestation. Rats were orally GMP treated from 3 days prior and during FA development. The severity of food anaphylaxis and diarrheal episodes, antibody production and histamine level were measured. Histopathological changes, inflammation and predominant cytokine profile at intestine were analyzed. Oral GMP intake decreased clinical signs and diarrhea severity induced by allergen, with a significant reduction in intestinal edema and expression level of

Topics: Allergens; Anaphylaxis; Animals; Anti-Allergic Agents; Caseins; Cytokines; Disease Models, Animal; Down-Regulation; Food Hypersensitivity; GATA3 Transcription Factor; Interleukin-13; Interleukin-1beta; Interleukin-5; Intestines; Male; Mast Cells; Ovalbumin; Peptide Fragments; Rats; Rats, Wistar

Immunoglobulin E (IgE)-mediated mast cell (MC) activation is crucial in multiple allergic diseases. Parkinson disease protein 7 (DJ-1) and Lyn kinase were reported as the receptor-proximal events in IgE receptor (FcεRI) signals in human MC. Kaempferol, a natural flavonol mainly derived from the rhizome of traditional Chinese herb Kaempferia galanga L. (Zingiberaceae), has been known to inhibit allergic reactions, but it was limited to the receptor-distal signals on rat basophilic leukemia cells. A thorough investigation of the inhibitory effects of kaempferol on human MC has not been done.. To investigate the inhibitory effects of kaempferol on IgE-mediated anaphylaxis in vivo and in human MCs, as well as the mechanism underlying its effects, especially the receptor-proximal signals.. IgE-mediated passive cutaneous anaphylaxis and systemic anaphylaxis model were applied to elucidate the antiallergic activity of kaempferol in vivo. The degranulation assay, calcium imaging, the release of cytokines and chemokines on the laboratory of allergic disease 2 (LAD2) cells were used to evaluate the antiallergic effect of kaempferol in vitro. Western blot analysis was performed to investigate the DJ-1/Lyn signaling pathway and downstream molecules. Kinase activity assay, immunofluorescence, and molecular docking were conducted to confirm the influence of kaempferol on DJ-1/Lyn molecules.. Kaempferol dose-dependently attenuated ovalbumin/IgE-induced mice paw swelling, primary MC activation from paw skin, as well as rehabilitated the hypothermia, and reduced the serum concentrations of histamine, tumor necrosis factor-alpha, interleukin-8, and monocyte chemo-attractant protein-1. Additionally, kaempferol suppressed IgE-mediated LAD2 cell degranulation and calcium fluctuation. Remarkably, kaempferol was found to bind with DJ-1 protein, and initially prevented DJ-1 from translocating to the plasma membrane, thereby inhibited full activation of Lyn, and eventually restrained those receptor-distal signaling molecules, involved Syk, Btk, PLCγ, IP3R, PKC, MAPKs, Akt and NF-κB.. Kaempferol could be used as a DJ-1 modulator for preventing MC-mediated allergic disorders through attenuating Lyn activation.

Topics: Anaphylaxis; Animals; Anti-Allergic Agents; Cell Degranulation; Cell Line; Dose-Response Relationship, Drug; Humans; Immunoglobulin E; Kaempferols; Male; Mast Cells; Mice, Inbred C57BL; Molecular Docking Simulation; Ovalbumin; Passive Cutaneous Anaphylaxis; Phospholipase C gamma; Protein Deglycase DJ-1; Receptors, IgE; Signal Transduction; src-Family Kinases

Viridicatol is a quinoline alkaloid isolated from the deep-sea-derived fungus

Topics: Anaphylaxis; Animals; Anti-Allergic Agents; Aquatic Organisms; B-Lymphocytes; beta-N-Acetylhexosaminidases; Calcium; Cell Line, Tumor; Disease Models, Animal; Food Hypersensitivity; Histamine; Hydroxyquinolines; Immunoglobulin E; Interleukin-10; Intestines; Mast Cells; Mice; Ovalbumin; Penicillium; Peptide Hydrolases; Quinolones; Rats; T-Lymphocytes, Regulatory; Tumor Necrosis Factor-alpha

Exposure to the widely-used phthalate plasticizer di-(2-ethylhexyl)-phthalate (DEHP) has been shown to be closely related to an increased prevalence of allergic diseases in infants and juveniles. Earlier work in our laboratory found that DEHP-related anaphylactic responses could be ascribed to T-follicular helper (T

Topics: Administration, Oral; Anaphylaxis; Animals; Animals, Newborn; Cell Differentiation; Child; Diethylhexyl Phthalate; Disease Models, Animal; Humans; Interleukin-4; Interleukins; Lymph Nodes; Mice; Ovalbumin; Plasticizers; Signal Transduction; Signaling Lymphocytic Activation Molecule Associated Protein; Signaling Lymphocytic Activation Molecule Family Member 1; T-Lymphocytes, Helper-Inducer; Weaning

The prevalence of IgE-mediated food allergy is increasing in the whole wide world which often causes skin and gastrointestinal tract symptoms, or even fatal anaphylactic shock. However, the evaluation of food allergens remains difficult, and the mechanism of food allergy is still not fully clear. To study the gene expression profile in food allergy animal models and identify the regulatory mechanism of the crucial genes, two administration routes were used to build animal models in our study. OVA-specific IgE and IL-4 levels were tested by ELISA, transcriptome profiling was carried out by microarray, and the regulatory mechanism of the highest expressed gene was studied in the primary spleen cells. We found that activation-induced cytidine deaminase (Aicda) is the highest expressed gene in the allergic mice, IL-21 can dramatically enhance the expression of Aicda in the lymph node microenvironment, and IL-17A can promote this effect significantly though it has only limited influence by itself. At last, we illuminated that the promotion of IL-21 on Aicda is partially through STAT3. In summary, our results suggest that IL-21 and IL-17A may play important role in the expression of Aicda as well as food allergy.

Topics: Allergens; Anaphylaxis; Animals; Cytidine Deaminase; Cytokines; Disease Models, Animal; Female; Food Hypersensitivity; Immunoglobulin E; Interleukins; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Ovalbumin; Spleen

Red algae sulfated polysaccharides (RASP) were extracted from

Topics: Anaphylaxis; Animals; Anti-Allergic Agents; Disease Models, Animal; Female; Histamine; Humans; Immunoglobulin E; Interferon-gamma; Interleukin-4; Mast Cells; Mice; Mice, Inbred BALB C; Ovalbumin; Polysaccharides; Rhodophyta; T-Lymphocytes, Regulatory; Tablets

Coumarin is an important organic heterocyclic compound with a wide range of sources in nature. It plays an important role in the drug discovery process due to its existence in diverse biologically active compounds and its broad bioactivity. In this study, the anti-allergic activity of coumarin was evaluated using an ovalbumin (OVA)-induced mouse food allergy model and an immunoglobulin (Ig)E mediated mouse bone marrow-derived mast cell (BMMC) model. Coumarin could alleviate the OVA-induced allergic symptoms, decrease the diarrhea rates, and promote the rectal temperature rise in allergic mice. Moreover, coumarin had the ability to reduce the levels of histamine and mouse mast cell proteinases, inhibit OVA-specific IgE, and significantly decrease the population of mast cells in the spleen and mesenteric lymph nodes. Coumarin could also significantly suppress mast cell-dependent passive cutaneous anaphylaxis. Additionally, the number of mature BMMCs was decreased as coumarin caused the suppression of c-KIT receptors. Furthermore, coumarin up-regulated the apoptosis of OVA-activated BMMCs in a concentration-dependent manner. In conclusion, coumarin displayed effective anti-food allergy activity via the regulation of mast cell function and numbers. Coumarin and its derivatives provide a new direction for the development of anti-food allergic drug components.

Topics: Anaphylaxis; Animals; Anti-Allergic Agents; Cell Line; Coumarins; Disease Models, Animal; Female; Food Hypersensitivity; Histamine; Immunoglobulin E; Mast Cells; Mice; Mice, Inbred BALB C; Ovalbumin; Passive Cutaneous Anaphylaxis; Spleen

Rush desensitization can provide short-term tolerance to individuals who are allergic to certain medications in instances where other therapeutic interventions are limited. While rush desensitization (DS) is typically successful in preventing adverse type I hypersensitivity reactions, the mechanism of allergic protection remains unknown. Given the rise in prevalence of individuals displaying multiple allergies, understanding the impact of rush DS on "bystander" allergens, or additional allergens to which an individual is sensitized, could help inform clinical recommendations.. To evaluate the effect of rush DS on bystander sensitization.. We used a murine model of rush DS, whereby BALB/c mice were sensitized to ovalbumin (OVA) and desensitized through repeated intraperitoneal injections of OVA. Using a local anaphylaxis assay, we measured ear swelling by Evans blue extravasation following intradermal challenge. In studies to measure the impact on bystander antigens, a modified protocol was used in which mice were dually sensitized to OVA and Keyhole limpet hemocyanin (KLH), and densensitized to either OVA or KLH prior to allergic challenge.. The immunological effects of rush DS were independent of changes in Th1 and Th2 cytokine production and circulating OVA-IgE levels. Instead, rush DS resulted in subclinical degranulation of mast cells prior to challenge. In our dual sensitization model, rush DS with a single antigen conferred protection against allergic challenge to a secondary antigen. Bystander protection required prior sensitization, as DS with an irrelevant antigen did not impact allergic responsiveness.. We reveal that a key mechanism of rush DS protection against allergic responsiveness may be the subclinical degranulation of mast cells. Therefore, performing rush DS to a single antigen to which one is IgE-sensitized may be sufficient to desensitize to multiple allergens. Future studies could lead to streamlined protocols of rush DS for patients with multiple allergies.

Topics: Allergens; Anaphylaxis; Animals; Antigens; Biomarkers; Cell Degranulation; Cytokines; Desensitization, Immunologic; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Female; Hypersensitivity; Immune Tolerance; Immunization; Immunoglobulin E; Mast Cells; Mice; Ovalbumin; T-Lymphocyte Subsets

The classical mast cells degranulation pathway is mediated by FcεRI aggregation and varies in strength among subjects. Dehydroandrographolide (DA) is one of principal components of Andrographis paniculata (Burm.f.) Nees (family: Acanthaceae) and considered the main contributors of its therapeutic properties, such as anti-tumor. In this study, inhibition of IgE-mediated anaphylactic reactions and anti-inflammatory potential of DA were investigated. The anti-anaphylactic activity of DA was investigated using skin swelling and extravasation assays in vivo and mast cell degranulation assay in vitro. The release of cytokines was measured using ELISA kits. Human Phospho-Kinase Array kit and western blotting were used to explore the related molecular signaling pathways. DA inhibited IgE-mediated mast cell activation, including degranulation and release of cytokines in vitro. Moreover, DA reduced the degree of swelling and Evans blue exudation of mice paw in a dose-dependent manner by inhibiting mast cell degranulation. DA obviously reduced the concentrations of histamine, TNF-α, MCP-1, IL-8, IL-13, and IL-4 in mice serum and inhibited IgE-mediated anaphylactic reactions as a potential P-PLCγ inhibitor. Our study reveals that DA can inhibit allergic responses in vivo and in vitro, and it may be regarded as a novel P-PLCγ inhibitor for preventing mast cell-immediate and delayed allergic diseases.

Topics: Anaphylaxis; Animals; Anti-Allergic Agents; Calcium Signaling; Cell Degranulation; Cell Line; Cytokines; Disease Models, Animal; Diterpenes; Enzyme Inhibitors; Histamine Release; Humans; Immunoglobulin E; Male; Mast Cells; Mice, Inbred C57BL; Ovalbumin; Phospholipase C gamma

Anaphylactic shock (AS) is a life-threatening, multisystem disorder arising from sudden release of mast cell- and basophil-derived mediators into the circulation. In this study, we have used a Wistar rat model to investigate AS-associated histopathologic changes in various organs. Rats were sensitized with ovalbumin (1 mg s.c), and AS was induced by intravenous injection of ovalbumin (1 mg). Experimental groups included nonallergic rats (n = 6) and allergic rats (n = 6). Heart rate and blood pressure were monitored during one hour. Organs were harvested at the end of the experiment and prepared for histologic and immunohistochemical studies. Lung, small bowel mucosa and spleen were found to undergo heavy infiltration by mast cells and eosinophils, with less prominent mast cell infiltration of cardiac tissue. The mast cells in lung, small bowel and spleen exhibited increased expression of tryptase, c-kit and induced nitric oxide synthase (iNOS). Increased expression of endothelial nitric oxide synthase (eNOS) by vascular endothelial cells was noted principally in lung, heart and small bowel wall. The Wistar rat model of AS exhibited accumulation of mast cells and eosinophils in the lung, small bowel, and spleen to a greater extent than in the heart. We conclude that lung and gut are principal inflammatory targets in AS, and likely contribute to the severe hypotension of AS. Targeting nitric oxide (NO) production may help reduce AS mortality.

Topics: Anaphylaxis; Animals; Disease Models, Animal; Hypotension; Inflammation; Injections, Intravenous; Injections, Subcutaneous; Male; Nitric Oxide; Ovalbumin; Rats; Rats, Wistar

Allergy is a major public health concern, the main treatment for which is symptomatic relief with anti-inflammatory drugs. A key clinical challenge is to induce specific tolerance in order to control allergen-specific memory B and T cells, and specifically block effector cell responses. Our lab recently developed antigen-specific regulatory T-cell (Treg) therapies as a treatment for adverse responses. Recently, we created a chimeric antigen receptor (CAR) approach in which we engineered a target protein antigen, ovalbumin (OVA), linked with the transmembrane and signal transduction domains, CD28-CD3ζ to directly target B cells and sensitized mast cells in an allergy model. We named this receptor "BAR" for B-cell Antibody Receptor. Murine or human Tregs, transduced with a BAR containing OVA or control Tregs expressing an unrelated antigen, were successfully expanded in vitro and tested in the murine OVA-alum allergy model with measurable titers of anti-OVA IgE. Because BAR Tregs express the target antigen and could interact with specific IgE on sensitized mast cells, we first demonstrated that intravenously injected OVA-BAR Tregs did not directly lead to a drop in temperature or release of mediators in plasma indicative of anaphylaxis. Forty-eight hours later, mice were challenged intraperitoneally with 200 μg OVA to induce an anaphylactic reaction, and temperature immediately measured for 30 min. We found that OVA-BAR Tregs protected mice from hypothermia, whereas mice given control BARs (expressing an unrelated antigen) or PBS showed substantial temperature drops indicative of anaphylaxis when systemically challenged with OVA. Importantly, this effect was also demonstrated in a passive anaphylaxis model in which mice that received anti-OVA IgE antibody were protected from hypothermia when treated with OVA-BAR Tregs prior to systemic OVA challenge. These results provide proof of principle that engineered allergen-specific T-regulatory cells can provide clinical protection against severe allergic reactions in individuals already IgE-sensitized to an allergen.

Topics: Allergens; Anaphylaxis; Animals; Female; Immune Tolerance; Immunization, Passive; Male; Mice; Mice, Inbred BALB C; Ovalbumin; T-Lymphocytes, Regulatory

Severe IgE-mediated, food-induced anaphylactic reactions are characterized by pulmonary venous vasodilatation and fluid extravasation, which are thought to lead to the life-threatening anaphylactic phenotype. The underlying immunologic and cellular processes involved in driving fluid extravasation and the severe anaphylactic phenotype are not fully elucidated.. We sought to define the interaction and requirement of IL-4 and vascular endothelial (VE) IL-4 receptor α chain (IL-4Rα) signaling in histamine-abelson murine leukemia viral oncogene homology 1 (ABL1)-mediated VE dysfunction and fluid extravasation in the severity of IgE-mediated anaphylactic reactions in mice.. Mice deficient in VE IL-4Rα and models of passive and active oral antigen- and IgE-induced anaphylaxis were used to define the requirements of the VE IL-4Rα and ABL1 pathway in severe anaphylactic reactions. The human VE cell line (EA.hy926 cells) and pharmacologic (imatinib) and genetic (short hairpin RNA knockdown of IL4RA and ABL1) approaches were used to define the requirement of this pathway in VE barrier dysfunction.. IL-4 exacerbation of histamine-induced hypovolemic shock in mice was dependent on VE expression of IL-4Rα. IL-4- and histamine-induced ABL1 activation in human VE cells and VE barrier dysfunction was ABL1-dependent. Development of severe IgE-mediated hypovolemia and shock required VE-restricted ABL1 expression. Treatment of mice with a history of food-induced anaphylaxis with the ABL kinase inhibitor imatinib protected the mice from severe IgE-mediated anaphylaxis.. IL-4 amplifies IgE- and histamine-induced VE dysfunction, fluid extravasation, and the severity of anaphylaxis through a VE IL-4Rα/ABL1-dependent mechanism. These studies implicate an important contribution by the VE compartment in the severity of anaphylaxis and identify a new pathway for therapeutic intervention of IgE-mediated reactions.

Topics: Allergens; Anaphylaxis; Animals; Antibodies; Cell Line; Endothelium, Vascular; Female; Histamine; Humans; Imatinib Mesylate; Immunoglobulin E; Interleukin-4; Male; Mice, Inbred BALB C; Mice, Transgenic; Ovalbumin; Proto-Oncogene Proteins c-abl; Receptors, Interleukin-4; Shock

We determined the renal responses to anaphylaxis and the effects of a nitric oxide synthesis inhibitor, L-NAME, in anesthetized rats and isolated perfused rat kidneys. After the ovalbumin antigen injection, the sensitized rats showed transient and substantial decreases in mean blood pressure and renal blood flow and an increase in renal vascular resistance. Creatinine clearance, a measure of renal function, decreased to 53% baseline at 2 h after antigen. L-NAME pretreatment significantly enhanced the antigen-induced renal vasoconstriction and renal dysfunction. Moreover, plasma creatinine levels significantly increased only in the L-NAME pretreated rats. Separately, in isolated perfused kidneys, we observed the antigen-induced renal vasoconstriction and its augmentation by L-NAME. In conclusion, the renal vascular response to the antigen is vasoconstriction, which is enhanced by L-NAME in both isolated perfused rat kidneys and anesthetized rats; it is accompanied by renal dysfunction, which is also augmented by L-NAME.

Topics: Anaphylaxis; Anesthesia; Animals; Hypotension; Kidney; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide; Ovalbumin; Rats; Rats, Sprague-Dawley; Vascular Resistance

Nanoparticle (NP)-based vaccines are attractive immunotherapy tools because of their capability to codeliver antigen and adjuvant to antigen-presenting cells. Their cellular distribution and serum protein interaction ("protein corona") after systemic administration and their effect on the functional properties of NPs is poorly understood.. We analyzed the relevance of the protein corona on cell type-selective uptake of dextran-coated NPs and determined the outcome of vaccination with NPs that codeliver antigen and adjuvant in disease models of allergy.. The role of protein corona constituents for cellular binding/uptake of dextran-coated ferrous nanoparticles (DEX-NPs) was analyzed both in vitro and in vivo. DEX-NPs conjugated with the model antigen ovalbumin (OVA) and immunostimulatory CpG-rich oligodeoxynucleotides were administered to monitor the induction of cellular and humoral immune responses. Therapeutic effects of this DEX-NP vaccine in mouse models of OVA-induced anaphylaxis and allergic asthma were assessed.. DEX-NPs triggered lectin-induced complement activation, yielding deposition of activated complement factor 3 on the DEX-NP surface. In the spleen DEX-NPs targeted predominantly B cells through complement receptors 1 and 2. The DEX-NP vaccine elicited much stronger OVA-specific IgG. Opsonization of lectin-coated NPs by activated complement components results in selective B-cell targeting. The intrinsic B-cell targeting property of lectin-coated NPs can be exploited for treatment of allergic immune responses.

Topics: Anaphylaxis; Animals; Antigens; B-Lymphocytes; Dextrans; Drug Carriers; Female; Ferrous Compounds; Hypersensitivity; Lectins; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Transgenic; Nanoparticles; Oligodeoxyribonucleotides; Ovalbumin; Protein Corona; T-Lymphocytes; Vaccines

Collagen peptides have been widely used as a food supplement. After ingestion of collagen peptides, oligopeptides containing hydroxyproline (Hyp), which are known to have some physiological activities, are detected in peripheral blood. However, the effects of collagen-peptide administration on immune response are unclear. In the present study, we tested the effects of collagen-peptide ingestion on allergic response and the effects of collagen-derived oligopeptides on CD4. BALB/c mice fed a collagen-peptide diet were immunized with ovalbumin (OVA), and their serum IgE and IgG levels, active cutaneous anaphylaxis, and cytokine secretion by splenocytes were examined. Naive CD4. In an active anaphylaxis model, oral administration of collagen peptides suppressed serum OVA-specific immunoglobulin E (IgE) production and diminished anaphylaxis responses. In this model, the ingestion of collagen peptides skewed the pattern of cytokine production by splenocytes toward T-helper (Th) type 1 and regulatory T (Treg) cells. In vitro T-helper cell differentiation assays showed that Hyp-containing oligopeptides promoted Th1 differentiation by upregulating IFN-γ-induced signal transducer and activator of transcription 1 (STAT1) signaling. These oligopeptides also promoted the development of Foxp3. Collagen-peptide ingestion suppresses allergic responses by skewing the balance of CD4

Topics: Administration, Oral; Anaphylaxis; Animals; Cell Differentiation; Collagen; Dietary Supplements; Disease Models, Animal; Humans; Immunoglobulin E; Lymphocyte Activation; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Ovalbumin; Peptides; T-Lymphocytes, Regulatory; Th1 Cells

Most of the patients develop food allergy early in life. The factors related to parental immune condition might be one of the conceivable causes.. We reported murine models of food allergy and oral OVA tolerance. To investigate the influence of parental immune condition on infant food allergy, female and male mice with food allergy or oral tolerance were mated with each other.. Food allergy was suppressed by decreased IgE production in the offspring of mice with food allergy. On the contrary, anaphylaxis for OVA was induced in the offspring of mice with oral tolerance. The suppression of food allergy being dependent on a maternal factor was revealed in the offspring after cross-mating mice with food allergy and oral tolerance. Because OVA-specific IgG, presumed to be from the allergic mother, was detected in the serum of naïve infants from mothers allergic to food, we assumed that the suppression was dependent on a specific IgG. The serum IgG purified by a G-protein column was administered before OVA sensitization in the food allergy model, and OVA-specific IgE production was found to be diminished in the administered mice. However, OVA-specific monoclonal IgG. We demonstrated that maternal specific IgG conjugated food antigen is an important factor related to the development of food allergy and acquiring tolerance.

Topics: Allergens; Anaphylaxis; Animals; Antigen-Antibody Complex; Disease Models, Animal; Female; Food Hypersensitivity; Immune Tolerance; Immunoglobulin A; Immunoglobulin E; Immunoglobulin G; Male; Mice, Inbred BALB C; Ovalbumin

Thymic stromal lymphopoietin (TSLP) is a regulator of mast cell-mediated allergic inflammatory reactions, but the manner in which TSLP contributes to allergic rhinitis (AR) remains unclear.. Here, we sought to determine that TSLP plays a crucial role in AR by interacting with Src-type tyrosine kinase p56lck and STAT6 and promoting mast cells degranulation.. The effects of TSLP on mast cell degranulation and AR were analysed in human mast cell line (HMC-1 cells), ovalbumin (OVA)-induced AR animal model, and human subjects. Small interfering RNA experiments were performed in HMC-1 cells and OVA-induced AR model. Immune responses were analysed by enzyme-linked immunosorbent assay, Western blotting, immunoprecipitation, and histological studies.. Thymic stromal lymphopoietin levels and mast cell-derived p56lck activation were elevated in human subjects with AR, and in AR mice, exogenous TSLP accelerated TH2-allergic inflammatory reactions by up-regulating p56lck and STAT6. On the other hand, depletion of TSLP, p56lck, and STAT6 ameliorated clinical symptoms in AR mice. The selective inhibitor of p56lck, damnacanthal, inhibits AR reactions.. Collectively, these observations suggest a role for TSLP/p56lck/STAT6 in AR and offer insight into potential therapeutic strategies.

Topics: Anaphylaxis; Animals; Cell Degranulation; Cell Differentiation; Cell Line; Cytokines; Disease Models, Animal; Humans; Lymphocyte Specific Protein Tyrosine Kinase p56(lck); Mast Cells; Mice; Mice, Knockout; Ovalbumin; Rhinitis, Allergic; STAT6 Transcription Factor; Th2 Cells; Thymic Stromal Lymphopoietin

Deep-sea-derived butyrolactone I (BTL-I), which was identified as a type of butanolide, was isolated from Aspergillus sp. Ovalbumin (OVA)-induced BALB/c anaphylaxis was established to explore the antifood allergic activity of BTL-I. As a result, BTL-I was able to alleviate OVA-induced allergy symptoms, reduce the levels of histamine and mouse mast cell proteinases, inhibit OVA-specific IgE, and decrease the population of mast cells in the spleen and mesenteric lymph nodes. BTL-I also significantly suppressed mast-dependent passive cutaneous anaphylaxis. Additionally, the maturation of bone marrow-derived mast cells (BMMCs) declined as BTL-I caused down-regulation of c-KIT receptors. Furthermore, molecular docking analyses revealed that BTL-I interacted with the inhibitory receptor, FcγRIIB. In conclusion, the reduction of mast cell function by deep-sea-derived BTL-I as well as its interactions with the inhibitory receptor, FcγRIIB, may contribute to BTL-I-related protection against food anaphylaxis.

Topics: 4-Butyrolactone; Anaphylaxis; Animals; Aspergillus; Cells, Cultured; Disease Models, Animal; Female; Food Hypersensitivity; Histamine; Humans; Immunoglobulin E; Mast Cells; Mice; Mice, Inbred BALB C; Ovalbumin; Proto-Oncogene Proteins c-kit; Seawater

Both probiotics and pathogens in the human gut express pathogen-associated molecular patterns (PAMPs) and die with the release of endotoxin and bacterial DNA, which can stimulate our immune system and cause immune reaction. However, it's interesting and fascinating to address why the normal intestinal flora will not generate immunological rejection like the pathogen does. By investigating the changes in cells and molecules relevant to immune tolerance in mice with ceftriaxone-induced dysbacteriosis, our study discovered that both the Evenness indexes and Shannon Wiener index of intestinal flora showed a decrease in dysbacteriosis mice. Moreover, the proportion of αβ

Topics: Allergens; Anaphylaxis; Animals; Anti-Bacterial Agents; Ceftriaxone; Cytokines; Dysbiosis; Gastrointestinal Microbiome; Immunoglobulin E; Intestines; Lymph Nodes; Male; Mice, Inbred BALB C; Ovalbumin; Peyer's Patches; Spleen; T-Lymphocytes, Regulatory

Cry1Ac toxin, from Bacillus thuringiensis, is widely used as a biopesticide and expressed in genetically modified (GM) plants used for human and animal consumption. Since Cry1Ac is also immunogenic and able to activate macrophages, it is crucial to thoroughly evaluate the immunological effects elicited after intra-gastric administration. The allergenic potential of purified Cry1Ac was assessed and compared with that induced in a murine model of food-allergy to ovalbumin (OVA), in which animals are sensitized with the adjuvant Cholera toxin (CT). Mice were weekly intragastrically administered with: i) vehicle phosphate-buffered saline (PBS), ii) OVA, iii) OVA plus CT iv) Cry1Ac or v) OVA plus Cry1Ac. Seven weeks after, mice were intragastrically challenged and allergic reactions along with diverse allergy related immunological parameters were evaluated at systemic and intestinal level. The groups immunized with, Cry1Ac, OVA/Cry1Ac or OVA/CT developed moderate allergic reactions, induced significant IgE response and increased frequencies of intestinal granulocytes, IgE+ eosinophils and IgE+ lymphocytes. These same groups also showed colonic lymphoid hyperplasia, notably in humans, this has been associated with food allergy and intestinal inflammation. Although the adjuvant and allergenic potential of CT were higher than the effects of Cry1Ac, the results show that applied intra-gastrically at 50 μg doses, Cry1Ac is immunogenic, moderately allergenic and able to provoke intestinal lymphoid hyperplasia. Moreover, Cry1Ac is also able to induce anaphylaxis, since when mice were intragastrically sensitized with increasing doses of Cry1Ac, with every dose tested, a significant drop in rectal temperature was recorded after intravenous challenge.

Topics: Allergens; Anaphylaxis; Animals; Bacillus thuringiensis; Bacillus thuringiensis Toxins; Bacterial Proteins; Disease Models, Animal; Endotoxins; Female; Food Hypersensitivity; Hemolysin Proteins; Humans; Immunization; Immunoglobulin E; Inflammation; Intestines; Mice; Mice, Inbred BALB C; Ovalbumin; Pest Control, Biological; Plants, Genetically Modified

Most allergic reactions are induced by mast cell activation. Mast cells play vital roles in the pathogenesis of allergic diseases. Bisdemethoxycurcumin (BDMC), a natural curcuminoid, has potential anti-allergic effects. Hence, we explored the effect of BDMC on mast cell-mediated allergic diseases. The study proved that BDMC suppresses β-hexosaminidase release, granule release, and membrane ruffling in monoclonal anti-2,4,6-dinitrophenyl-immunoglobulin (Ig) E/human serum albumin (DNP-IgE/HSA)-stimulated rat basophilic leukaemia cells (RBL-2H3 cells), and BDMC suppressed ovalbumin (OVA)-induced allergic rhinitis (AR) symptoms and OVA-specific IgE levels in AR mice. Furthermore, BDMC increased the survival of compound 48/80 anaphylaxis shock mice and elevated the decreased rectal temperature in OVA-induced active systemic anaphylaxis mice. These findings indicate that BDMC regulates the degranulation of mast cells, demonstrating its potential in the treatment of mast cell-induced allergic reactions.

Topics: Anaphylaxis; Animals; Cell Line; Curcumin; Diarylheptanoids; Hypersensitivity; Male; Mast Cells; Mice; Mice, Inbred BALB C; Ovalbumin; p-Methoxy-N-methylphenethylamine; Rats; Rhinitis, Allergic

Anaphylactic shock is life-threatening, but pathophysiology of the stomach lesion remains unclear. We determined gastric hemodynamics and gastric functions during anaphylactic hypotension, as compared to hypotension induced by hemorrhage or sodium nitroprusside (SNP) in anesthetized and ovalbumin-sensitized Sprague-Dawley rats. Systemic arterial pressure, portal venous pressure, and gastric arterial blood flow were measured, and gastric vascular resistance (GVR) was determined. Separately, the intragastric pressure (IGP) and gastric effluent, as a measure of gastric flux, were continuously measured. During anaphylaxis, GVR decreased only transiently at 0.5 min, followed by an increase. IGP increased markedly, while gastric flux decreased. During hemorrhage, GVR and IGP increased, while gastric flux did not change. When SNP was injected, both GVR and IGP decreased and gastric flux increased only just after injection. In conclusion, gastric vasodilatation occurs only transiently after antigen injection, and gastric motility increases, but gastric emptying deceases during anaphylactic hypotension in anesthetized rats.

Topics: Anaphylaxis; Anesthesia; Animals; Arterial Pressure; Gastric Emptying; Gastrointestinal Motility; Hemodynamics; Hemorrhage; Hypotension; Male; Nitroprusside; Ovalbumin; Portal Pressure; Rats; Rats, Sprague-Dawley; Stomach; Vascular Resistance; Vasodilation; Vasodilator Agents

Cardiac anaphylaxis is one of the features of anaphylactic hypotension. Patients treated with propranolol, a nonselective β-adrenoceptor (AR) antagonist, develop severe anaphylaxis, but the mechanism remains unknown. Under examination were the effects of β1- and β2-AR antagonist on anaphylaxis-induced coronary vasoconstriction and cardiac dysfunction in isolated blood-perfused rat hearts.. Isolated hearts from ovalbumin-sensitized Wistar rats were subjected to coronary perfusion with blood at a constant pressure and measurements were made of coronary blood flow and left ventricu-lar (LV) pressure. Following pretreatment with selective β2-AR antagonist ICI118,551 or selective β1-AR antagonist atenolol, cardiac anaphylaxis was induced by intracoronary injections of ovalbumin antigen. LV contractility was evaluated by the maximum increasing rate of systolic LV pressure (dP/dtmax).. In response to antigen administrations, ICI118,551 pretreated hearts showed a greater de-crease in coronary blood flow and consequently a greater increase in coronary vascular resistance than the atenolol pretreated hearts. Pretreatment with ICI118,551 caused a greater decrease in dP/dtmax than those with atenolol.. Cardiac anaphylaxis-induced contractile dysfunction and coronary spasm are severe in b2-, rather than β1-AR antagonist, pretreated isolated blood-perfused rat hearts.

Topics: Adrenergic beta-1 Receptor Antagonists; Adrenergic beta-2 Receptor Antagonists; Anaphylaxis; Animals; Atenolol; Coronary Vasospasm; Coronary Vessels; Disease Models, Animal; Isolated Heart Preparation; Male; Myocardial Contraction; Ovalbumin; Propanolamines; Rats, Wistar; Receptors, Adrenergic, beta-1; Receptors, Adrenergic, beta-2; Time Factors; Vasoconstriction; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Pressure

Anaphylactoid reactions, accounting for more than 77% of all immune-mediated immediate hypersensitivity reactions, have become a serious threat to public health, but their effect mechanism is not clear and diagnostic tests are limited. Comprehensive metabolite analysis may reveal the anaphylactoid effect mechanism systematically and provide reference for future diagnostic purposes.. Plasma from Brown Norway rats given intravenous injection of saline, compound 48/80 (2.5 mL/kg) or ovalbumin (20 mL/kg) in 20 s for the first time was used to study the effect mechanism of anaphylactoid reactions through metabolomics (UPLC-qTOF-MS/MS). Metabolomics integrated with proteomics data were used to analyze the anaphylactoid pathways by MetaboAnalyst followed by integrated pathway analysis.. Thirty metabolites were identified through the METLIN database by MS/MS and 18 of them were confirmed by authentic standards. The results showed that adenosine, histamine, N-acetylhistamine, N(α)-γ-glutamylhistamine, malate and xanthine are important indices for anaphylactoid reactions. It could be concluded that the effect mechanism is mainly composed of histidine metabolism, arachidonic acid metabolism, energy metabolism, purine metabolism and other small molecules through 30 metabolites. Multiple linear regression analysis indicated that not only histamine but also N(α)-γ-glutamylhistamine and arachidonic acid could be used to evaluate anaphylactoid symptoms of animals. Furthermore, the citrate cycle, histidine metabolism and arachidonic acid metabolism could be the main pathways of anaphylactoid reactions as determined by MetaboAnalyst.. The results may provide a reference to improve diagnostic accuracy and predict and monitor treatment efficacy in anaphylactoid reactions in the clinical setting.

Topics: Allergens; Anaphylaxis; Animals; Arachidonic Acid; Citric Acid; Disease Models, Animal; Histamine; Humans; Hypersensitivity; Male; Metabolomics; Ovalbumin; Proteomics; Rats; Rats, Inbred BN; Signal Transduction; Tandem Mass Spectrometry

The two life-threatening signs of anaphylactic shock (AS) are severe arterial hypotension and bronchospasm. Guidelines recommend epinephrine as first-line treatment. Arginine vasopressin (AVP) has been proposed as an alternative if epinephrine does not correct arterial hypotension. These two drugs may have beneficial, neutral or deleterious effects on airflow either directly or by modifying factors that regulate vasodilatation and/or edema in the bronchial wall.. To compare the effects of epinephrine and AVP on airflow and airway leakage in a rat model of AS.. Thirty-two ovalbumin-sensitized rats were randomized into four groups: control (CON), AS without treatment (OVA), AS treated with epinephrine (EPI), and AS treated with AVP (AVP). Mean arterial pressure (MAP), respiratory resistance and elastance and microvascular leakage in the airways were measured.. All OVA rats died within 20 minutes following ovalbumin injection. Ovalbumin induced severe arterial hypotension and airway obstruction (221 ± 36 hPa.s.L. Epinephrine was superior to AVP for alleviating the airway response in a rat model of AS. When bronchospasm and severe arterial hypotension are present during AS, epinephrine should be the drug of choice.

Topics: Airway Obstruction; Anaphylaxis; Animals; Arterial Pressure; Bronchial Spasm; Capillary Leak Syndrome; Epinephrine; Hypotension; Neurophysins; Ovalbumin; Protein Precursors; Rats; Respiratory System; Vasopressins

Currently, there are no efficient medications available for the prevention and treatment of food allergy (FA). Herbal medicines, including traditional Japanese Kampo medicines (TJKMs), are promising therapeutic drugs.. We screened 18 TJKMs for treatment of FA symptoms in a mouse FA model induced by ovalbumin (OVA). BALB/c mice were sensitized intraperitoneally by an OVA/aluminum hydroxide gel mixture followed by 4 booster doses of oral OVA and FA symptom induction by 50 mg of OVA. TJKMs were orally administered for 28 days from the day of sensitization to the day before FA symptom induction. Evaluated FA symptoms included a decrease in body temperature and allergic diarrhea. Allergic sensitization was determined by plasma OVA-specific IgE levels. Cytokine mRNA levels in mesenteric lymph nodes, plasma mouse mast cell protease-1, and the number of mast cells in the small and large intestines were analyzed. Additionally, the therapeutic effect of the TJKM eppikajutsuto (EJT) on mast cell degranulation was determined in active anaphylaxis and passive cutaneous anaphylaxis models.. EJT effectively prevented FA symptoms. Although OVA-specific IgE levels and the intestinal mast cell numbers were not different between the EJT-treated and untreated FA mice, plasma mMcpt1 and IL-4 levels were lower in EJT-treated FA mice than untreated FA mice. EJT could alleviate symptoms in both active and passive anaphylaxis models.. EJT prevented OVA-induced FA symptoms in a mouse model, suggesting that EJT might exert its therapeutic activity via IL-4 suppression and the inhibition of mucosal mast cell degranulation.

Topics: Allergens; Anaphylaxis; Animals; Anti-Allergic Agents; Cell Degranulation; Cytokines; Disease Models, Animal; Female; Food Hypersensitivity; Immunoglobulin E; Intestinal Mucosa; Male; Mast Cells; Medicine, Kampo; Mice, Inbred BALB C; Mice, Inbred ICR; Ovalbumin; Peptide Hydrolases; Pharmaceutical Preparations; Plant Extracts; RNA, Messenger

Diospyros kaki L. (Ebenaceae) fruit is widely distributed in Asia and is known to exert anti-inflammatory and antithrombotic effects.. We evaluated the inhibitory effect of aqueous extract of D. kaki calyx (AEDKC) on mast cell-mediated immediate-type hypersensitivity and underlying mechanism of action.. For in vivo, ovalbumin (OVA)-induced active systemic anaphylaxis (ASA) and immunoglobulin (Ig) E-mediated passive cutaneous anaphylaxis (PCA) models were used. In the ASA, AEDKC (1-100 mg/kg) was orally administered 3 times during 14 days. In the PCA, AEDKC was orally treated 1 h before the antigen challenge. The control drug dexamethasone was used to compare the effectiveness of AEDKC. For in vitro, IgE-stimulated RBL-2H3 cells and primary cultured peritoneal mast cells were used to determine the role of AEDKC (0.01-1 mg/mL).. Oral administration of AEDKC dose dependently suppressed rectal temperature decrease and increases in serum histamine, total IgE, OVA-specific IgE, and interleukin (IL)-4 in the ASA. In the PCA, AEDKC reduced Evans blue pigmentation. Compared to dexamethasone (10 mg/kg), AEDKC (100 mg/kg) showed similar inhibitory effects in vivo. AEDKC concentration dependently suppressed the release of histamine and β-hexosaminidase through the reduction of intracellular calcium in mast cells. In addition, AEDKC decreased the expression and secretion of tumour necrosis factor-α and IL-4 by the reduction of nuclear factor-κB. The inhibitory potential of AEDKC (1 mg/mL) was similar with dexamethasone (10 μM) in vitro.. We suggest that AEDKC may be a potential candidate for the treatment of mast cell-mediated allergic diseases.

Topics: Anaphylaxis; Animals; Cell Survival; Cells, Cultured; Diospyros; Dose-Response Relationship, Drug; Hypersensitivity; Male; Mast Cells; Mice; Mice, Inbred ICR; Ovalbumin; Plant Extracts; Rats; Rats, Sprague-Dawley

The attempt to induce oral tolerance as a treatment for food allergy has been hampered by a lack of sustained clinical protection. Immunotherapy by nonoral routes, such as the skin, may be more effective for the development of maintained tolerance to food allergens.. We sought to determine the efficacy and mechanism of tolerance induced by epicutaneous immunotherapy (EPIT) in a model of food-induced anaphylaxis.. C3H/HeJ mice were sensitized to ovalbumin (OVA) orally or through the skin and treated with EPIT using OVA-Viaskin patches or oral immunotherapy using OVA. Mice were orally challenged with OVA to induce anaphylaxis. Antigen-specific regulatory T (Treg)-cell induction was assessed by flow cytometry using a transgenic T-cell transfer model.. By using an adjuvant-free model of food allergy generated by epicutaneous sensitization and reactions triggered by oral allergen challenge, we found that EPIT induced sustained protection against anaphylaxis. We show that the gastrointestinal tract is deficient in de novo generation of Treg cells in allergic mice. This defect was tissue-specific, and epicutaneous application of antigen generated a population of gastrointestinal-homing LAP. Our data highlight the immune communication between skin and gastrointestinal tract, and identifies novel mechanisms by which epicutaneous tolerance can suppress food-induced anaphylaxis.

Topics: Administration, Cutaneous; Allergens; Anaphylaxis; Animals; Arachis; Cholera Toxin; Desensitization, Immunologic; Food Hypersensitivity; Forkhead Transcription Factors; Immunoglobulin G; Mice, Inbred BALB C; Mice, Inbred C3H; Ovalbumin; Peptides; T-Lymphocytes, Regulatory; Transforming Growth Factor beta

Mast cells are important effector cells in immunoglobulin (Ig) E-mediated allergic reactions such as asthma, atopic dermatitis and rhinitis. Vanillic acid, a natural product, has shown anti-oxidant and anti-inflammatory activities. In the present study, we investigated the anti-allergic inflammatory effects of ortho-vanillic acid (2-hydroxy-3-methoxybenzoic acid, o-VA) that was a derivative of vanillic acid isolated from Amomum xanthioides. In mouse anaphylaxis models, oral administration of o-VA (2, 10, 50 mg/kg) dose-dependently attenuated ovalbumin-induced active systemic anaphylaxis and IgE-mediated cutaneous allergic reactions such as hypothermia, histamine release, IgE production and vasodilation; administration of o-VA also suppressed the mast cell degranulator compound 48/80-induced anaphylaxis. In cultured mast cell line RBL-2H3 and isolated rat peritoneal mast cells in vitro, pretreatment with o-VA (1-100 μmol/L) dose-dependently inhibited DNP-HSA-induced degranulation of mast cells by decreasing the intracellular free calcium level, and suppressed the expression of pro-inflammatory cytokines TNF-α and IL-4. Pretreatment of RBL-2H3 cells with o-VA suppressed DNP-HSA-induced phosphorylation of Lyn, Syk, Akt, and the nuclear translocation of nuclear factor-κB. In conclusion, o-VA suppresses the mast cell-mediated allergic inflammatory response by blocking the signaling pathways downstream of high affinity IgE receptor (FcεRI) on the surface of mast cells.

Topics: Anaphylaxis; Animals; Benzoates; Calcium; Cell Degranulation; Cells, Cultured; Dinitrophenols; Dose-Response Relationship, Drug; Hypersensitivity; Immunoglobulin E; Inflammation Mediators; Male; Mast Cells; Mice; NF-kappa B; Ovalbumin; p-Methoxy-N-methylphenethylamine; Phosphorylation; Rats; Receptors, IgE; Serum Albumin; Signal Transduction; Vanillic Acid

The prevalence of food allergies worldwide has increased recently. Epicutaneous sensitization to antigen could be a method to study food allergy. To clarify the mechanisms of food allergy, we established a mouse model of epicutaneous sensitization using ovalbumin (OVA). BALB/c mice were sensitized by three-time application of OVA to tape-stripped skin (1-week sensitization at 2-week intervals) and oral challenge of OVA undertaken. Rectal temperature was monitored. Blood and tissue (skin and jejunum) of challenged mice were taken. Numbers of mast cells (MCs) and basophils were counted. Serum and/or tissue levels of OVA -specific IgE and IgG antibodies and several cytokines were measured using enzyme-linked immunoassay kits. MC and basophil depletion experiments were undertaken. In OVA/epicutaneous-sensitized and orally challenged mice, systemic anaphylaxis (as evidenced by reduced rectal temperature) was observed. Levels of OVA-specific IgE and IgG antibodies were increased in these mice, as were increased number of MCs and basophils. Serum levels of MC protease 1 were increased significantly. Basophil and MC depletion experiments revealed that they both participate in reactions. Increased production of thymic stromal lymphopoietin (TSLP) at skin sites of OVA sensitization was noted. We speculate that TSLP produced from epidermal cells during antigen sensitization can enable basophils to promote a T helper (Th)2 immune reaction, leading to and systemic anaphylaxis by antigen-specific IgE-bearing MCs. This TSLP-basophils-MC axis could be a novel therapeutic target against food allergy.

Topics: Anaphylaxis; Animals; Basophils; Cytokines; Food Hypersensitivity; Jejunum; Mast Cells; Mice, Inbred BALB C; Ovalbumin; Skin; Thymic Stromal Lymphopoietin

We herein established a new method to evaluate allergic responses in mice rapidly and easily with ethical improvement by reducing the number of animals used. A single intravenous injection of a mixture of anti-OVA monoclonal IgE and fluorescein-ovalbumin (FITC-OVA) induced the distinctive spotted distribution of FITC-OVA in skin, named "ASDIS (Anaphylaxis-dependent Spotted Distribution of a fluorescent-labeled Immune complex in Skin)", and this was easily detected by in vivo imaging. The parallel induction of hypothermia, scratching, serum histamine increases, and ASDIS as well as the inhibition of ASDIS by either the systemic administration of a histamine H1 receptor antagonist or mast cell-depleting antibody suggested that our method, which only required 15 min, induced these allergic responses including ASDIS. Relatively mild but significant ASDIS was induced also in mice with passive systemic anaphylaxis by the method, requiring 2 separate days. The painting of anti-histamines on the skin markedly reduced ASDIS in the painted area only, suggesting the potential of this model to simultaneously compare the anti-allergic effects of several candidate compounds with control drugs in the same mice. ASDIS was suggested to originate from extravasated FITC-OVA/OE-1 immune complexes from blood to skin tissues other than mast cells. Our new method has the advantages of rapidity, easy method, and lower animal numbers to evaluate anti-allergic compounds as well as the characteristics of the used antibody, antigen, labeling molecules, additives, and other formulations. Our model for inducing ASDIS may contribute to the development of anti-allergic drugs, especially those intended for application to the skin.

Topics: Administration, Topical; Allergens; Anaphylaxis; Animals; Anti-Allergic Agents; Antigen-Antibody Complex; Fluorescence; Immunoglobulin E; Injections, Intravenous; Mice; Mice, Hairless; Mice, Inbred DBA; Ovalbumin; Skin

To assess modifications in baseline specific IgE- and anti-IgE- and antigen-specific-mediated basophil activation in egg-allergic children. The values were compared before and after the children completed specific oral tolerance induction (SOTI) with egg.. We studied 28 egg-allergic children who completed SOTI with egg. The basophil activation test and specific IgE determinations with egg white, ovalbumin, and ovomucoid were performed in all 28 children.. A decrease in antigen-specific activation with egg white, ovalbumin, and ovomucoid was observed only at the 2 lowest concentrations used (5 and 0.05 ng/mL). Baseline activation was higher in patients with multiple food allergies and in those who developed anaphylaxis during SOTI; this activation decreased in both groups after completion of SOTI. A significant decrease was also observed in specific IgE values for egg white, ovalbumin, and ovomucoid after tolerance induction.. Food tolerance induction is a specific process for each food that can be mediated by immunologic changes such as a decrease in specific IgE values and in specific and spontaneous basophil activation.

Topics: Anaphylaxis; Antigens; Basophils; Biomarkers; Child; Child, Preschool; Desensitization, Immunologic; Dose-Response Relationship, Immunologic; Egg Hypersensitivity; Egg White; Female; Humans; Immune Tolerance; Immunoglobulin E; Intradermal Tests; Male; Monitoring, Immunologic; Ovalbumin; Ovomucin; Predictive Value of Tests; Treatment Outcome

Cutaneous exposure to food allergens predisposes to food allergy, which is commonly associated with atopic dermatitis (AD). Levels of the epithelial cytokine IL-33 are increased in skin lesions and serum of patients with AD. Mast cells (MCs) play a critical role in food-induced anaphylaxis and express the IL-33 receptor ST2. The role of IL-33 in patients with MC-dependent food anaphylaxis is unknown.. We sought to determine the role and mechanism of action of IL-33 in patients with food-induced anaphylaxis in a model of IgE-dependent food anaphylaxis elicited by oral challenge of epicutaneously sensitized mice.. Wild-type, ST2-deficient, and MC-deficient Kit. Il33 mRNA expression was upregulated in tape-stripped mouse skin and scratched human skin. Tape stripping caused local and systemic IL-33 release in mice. ST2 deficiency, as well as ST2 blockade before oral challenge, significantly reduced the severity of oral anaphylaxis without affecting the systemic T. IL-33 is released after mechanical skin injury, enhances IgE-mediated MC degranulation, and promotes oral anaphylaxis after epicutaneous sensitization by targeting MCs. IL-33 neutralization might be useful in treating food-induced anaphylaxis in patients with AD.

Topics: Administration, Cutaneous; Allergens; Anaphylaxis; Animals; Dermatitis, Atopic; Female; Food Hypersensitivity; Humans; Immunoglobulin E; Interleukin-33; Mast Cells; Mice, Inbred BALB C; Mice, Transgenic; Ovalbumin; RNA, Messenger; Skin

The present study evaluated the immunomodulatory effects of chelidonic acid, a secondary plant metabolite, with therapeutic potential in allergic disorders, in experimental animals. In mast cell degranulation studies, ovalbumin immunized and challenged rats, chelidonic acid (1, 3 and 10mg/kg, i.p.) dose relatedly prevented ovalbumin challenge induced mast cell degranulation by differing degrees when compared with vehicle treated group, and these effects were comparable with prednisolone (10mg/kg). A reduction in post-challenge mortality was also observed in all treated groups. Further, there were reductions in the blood eosinophil counts and serum IgE levels after chelidonic acid treatment. Chelidonic acid also inhibited histamine release from rat peritoneal mast cells (RPMC) in vitro, in a dose related manner. In tests for adaptive immunity, in rats immunized with sheep RBC, chelidonic acid differentially suppressed the (a) plaque forming cell (PFC) count in rat splenic cells, (b) anti-SRBC antibody titre and serum IgG levels and (c) increases in foot pad thickness in the DTH assay - all of which were comparable with prednisolone. These experimental results are discussed in light of the possible therapeutic potential of chelidonic acid in allergic disorders.

Topics: Adaptive Immunity; Allergens; Anaphylaxis; Animals; Cell Degranulation; Cells, Cultured; Erythrocytes; Hemolytic Plaque Technique; Histamine Release; Hypersensitivity, Delayed; Immunoglobulin E; Immunoglobulin G; Immunologic Factors; Mast Cells; Ovalbumin; Pyrans; Rats, Wistar; Sheep; Spleen

Adverse reactions of injectable drugs usually occur at first administration and are closely associated with the dosage and speed of injection. This phenomenon is correlated with the anaphylactoid reaction. However, up to now, study methods based on antigen detection have still not gained wide acceptance and single physiological indicators cannot be utilized to differentiate anaphylactoid reactions from allergic reactions and inflammatory reactions. In this study, a reliable method for the evaluation of anaphylactoid reactions caused by injectable drugs was established by using multiple physiological indicators. We used compound 48/80, ovalbumin and endotoxin as the sensitization agents to induce anaphylactoid, allergic and inflammatory reactions. Different experimental animals (guinea pig and nude rat) and different modes of administration (intramuscular, intravenous and intraperitoneal injection) and different times (15 min, 30 min and 60 min) were evaluated to optimize the study protocol. The results showed that the optimal way to achieve sensitization involved treating guinea pigs with the different agents by intravenous injection for 30 min. Further, seven related humoral factors including 5-HT, SC5b-9, Bb, C4d, IL-6, C3a and histamine were detected by HPLC analysis and ELISA assay to determine their expression level. The results showed that five of them, including 5-HT, SC5b-9, Bb, C4d and IL-6, displayed significant differences between anaphylactoid, allergic and inflammatory reactions, which indicated that their combination could be used to distinguish these three reactions. Then different injectable drugs were used to verify this method and the results showed that the chosen indicators exhibited good correlation with the anaphylactoid reaction which indicated that the established method was both practical and reliable. Our research provides a feasible method for the diagnosis of the serious adverse reactions caused by injectable drugs which could be used in the clinical practice.

Topics: Anaphylaxis; Animals; Biomarkers; Chromatography, High Pressure Liquid; Complement Membrane Attack Complex; Drug Hypersensitivity; Endotoxins; Guinea Pigs; Histamine; Injections, Intravenous; Interleukin-6; Ovalbumin; Rats; Serotonin; Time Factors

In our mouse model, gastric acid-suppression is associated with antigen-specific IgE and anaphylaxis development. We repeatedly observed non-responder animals protected from food allergy. Here, we aimed to analyse reasons for this protection. Ten out of 64 mice, subjected to oral ovalbumin (OVA) immunizations under gastric acid-suppression, were non-responders without OVA-specific IgE or IgG1 elevation, indicating protection from allergy. In these non-responders, allergen challenges confirmed reduced antigen uptake and lack of anaphylactic symptoms, while in allergic mice high levels of mouse mast-cell protease-1 and a body temperature reduction, indicative for anaphylaxis, were determined. Upon OVA stimulation, significantly lower IL-4, IL-5, IL-10 and IL-13 levels were detected in non-responders, while IL-22 was significantly higher. Comparison of fecal microbiota revealed differences of bacterial communities on single bacterial Operational-Taxonomic-Unit level between the groups, indicating protection from food allergy being associated with a distinct microbiota composition in a non-responding phenotype in this mouse model.

Topics: Administration, Oral; Allergens; Anaphylaxis; Animals; Anti-Ulcer Agents; Bacteria; Cytokines; Disease Models, Animal; Feces; Female; Food Hypersensitivity; Gastric Acid; Immunization; Immunoglobulin A; Immunoglobulin E; Immunoglobulin G; Intestines; Mice, Inbred BALB C; Microbiota; Ovalbumin; Spleen; Stomach; Sucralfate

Allergen-specific immunotherapy (ASIT) is used to treat the symptoms of immediate type I hypersensitivity. The mechanisms driving establishment of allergen tolerance are not yet fully understood.. The goal of this study was to develop and immunologically characterize 3 murine models of ASIT to simulate protocols currently used to treat patients with type I hypersensitivities.. Ovalbumin (OVA)-sensitized mice were desensitized to OVA by means of repeated injections of OVA with a rapid, intermediate, or gradual protocol. After desensitization, mice were assessed for clinical sensitivity to OVA, and immunologic parameters were assessed.. Mice in all treatment protocols displayed decreased vascular permeability in response to OVA challenge after desensitization. Circulating OVA-specific IgE levels, as well as basophil activation in response to OVA stimulation and IgE cross-linking, were significantly decreased in all treatment groups. Intermediate and gradual protocols, but not rapid desensitization, suppressed splenocyte proliferation and production of IL-4, IL-5, and IFN-γ in response to OVA and polyclonal activation. Similarly, significant increases in IL-10 production, numbers of CD4(+)CD25(+) forkhead box protein 3-positive regulatory T cells, and OVA-specific IgG1 antibody levels were only observed in mice undergoing prolonged ASIT regimens.. Suppression of IgE-mediated activation is a common feature of all desensitization schedules. Induction of immunoregulatory networks requires prolonged desensitization schedules.

Topics: Allergens; Anaphylaxis; Animals; Basophils; Cytokines; Desensitization, Immunologic; Disease Models, Animal; Female; Hypersensitivity, Immediate; Immunoglobulin Isotypes; Immunomodulation; Mice; Ovalbumin; Spleen; T-Lymphocyte Subsets; T-Lymphocytes, Regulatory

Salivary glands are involved in the production and exocrine and endocrine secretion of biologically active proteins, polypeptides, and hormones involved in growth and differentiation, homeostasis, and digestion. We have previously studied the prohormone submandibular rat 1 (SMR1), product of the Vcsa1 gene, which is highly expressed in the testes and salivary glands of rats, and can be cleaved to produce polypeptides with analgesic, erectile function, and anti-inflammatory activities. Humans lack the Vcsa1 gene, but homologous sequences and functions for analgesia and erectile function exist in the human genes Prol1, SMR3a, and SMR3b located on the human chromosomal region close to where Vcsa1 lies in the rat. Here we show the human protein calcium-binding protein spermatid-specific 1 (CABS1) contains a similar sequence to the anti-inflammatory sequence in rat SMR1, thus CABS1 may be another human gene with homologous function to Vcsa1. Using Western blot and PCR, we discovered that the human protein CABS1, previously thought to only be expressed in the testes, is also expressed in the salivary glands and lung, in a tissue-specific manner. Peptides derived from CABS1 were tested in an in vivo mouse model of lipopolysaccharide (LPS)-induced neutrophilia and an ex vivo rat model of antigen-induced intestinal anaphylaxis and significantly reduced both neutrophil accumulation in bronchoalveolar lavage fluid and antigen-induced ileal contractions, respectively. Thus human CABS1 has a peptide motif homologous to the anti-inflammatory peptide sequence of rat SMR1. Whether this similarity of CABS1 extends to the neuroendocrine regulation of the anti-inflammatory activity seen for SMR1 remains to be determined.

Topics: Amino Acid Motifs; Anaphylaxis; Animals; Anti-Inflammatory Agents; Calcium-Binding Proteins; Disease Models, Animal; Dose-Response Relationship, Drug; Gene Expression Regulation; Humans; Lipopolysaccharides; Male; Mice, Inbred BALB C; Neutrophil Infiltration; Neutrophils; Ovalbumin; Peptide Fragments; Pneumonia; Protein Precursors; Rats, Sprague-Dawley; RNA, Messenger; Salivary Glands; Salivary Proteins and Peptides

The release of mediators by mast cells triggers allergic symptoms involving various physiological systems and, in the most severe cases, the development of anaphylactic shock compromising mainly the nervous and cardiovascular systems. We aimed to establish variables to objectively study the anaphylactic response (AR) after an oral challenge in an allergy model. Brown Norway rats were immunized by intraperitoneal injection of ovalbumin with alum and toxin from Bordetella pertussis. Specific immunoglobulin (Ig) E antibodies were developed in immunized animals. Forty days after immunization, the rats were orally challenged with the allergen, and motor activity, body temperature and serum mast cell protease concentration were determined. The anaphylaxis induced a reduction in body temperature and a decrease in the number of animal movements, which was inversely correlated with serum mast cell protease release. In summary, motor activity is a reliable tool for assessing AR and also an unbiased method for screening new anti-allergic drugs.

Topics: Allergens; Anaphylaxis; Animals; Body Temperature; Disease Models, Animal; Female; Immunoglobulin E; Motor Activity; Ovalbumin; Peptide Hydrolases; Rats; Serine Endopeptidases

IgE antibodies and mast cells play critical roles in the establishment of allergic responses to food antigens. Curcumin, the active ingredient of the curry spice turmeric, has anti-inflammatory properties, and thus may have the capacity to regulate Th2 cells and mucosal mast cell function during allergic responses. We assessed whether curcumin ingestion during oral allergen exposure can modulate the development of food allergy using a murine model of ovalbumin (OVA)-induced intestinal anaphylaxis. Herein, we demonstrate that frequent ingestion of curcumin during oral OVA exposure inhibits the development of mastocytosis and intestinal anaphylaxis in OVA-challenged allergic mice. Intragastric (i.g.) exposure to OVA in sensitized BALB/c mice induced a robust IgE-mediated response accompanied by enhanced OVA-IgE levels, intestinal mastocytosis, elevated serum mMCP-1, and acute diarrhea. In contrast, mice exposed to oral curcumin throughout the experimental regimen appeared to be normal and did not exhibit intense allergic diarrhea or a significant enhancement of OVA-IgE and intestinal mast cell expansion and activation. Furthermore, allergic diarrhea, mast cell activation and expansion, and Th2 responses were also suppressed in mice exposed to curcumin during the OVA-challenge phase alone, despite the presence of elevated levels of OVA-IgE, suggesting that curcumin may have a direct suppressive effect on intestinal mast cell activation and reverse food allergy symptoms in allergen-sensitized individuals. This was confirmed by observations that curcumin attenuated the expansion of both adoptively transferred bone marrow-derived mast cells (BMMCs), and inhibited their survival and activation during cell culture. Finally, the suppression of intestinal anaphylaxis by curcumin was directly linked with the inhibition of NF-κB activation in curcumin-treated allergic mice, and curcumin inhibited the phosphorylation of the p65 subunit of NF-κB in BMMCs. In summary, our data demonstrates a protective role for curcumin during allergic responses to food antigens, suggesting that frequent ingestion of this spice may modulate the outcome of disease in susceptible individuals.

Topics: Anaphylaxis; Animals; Curcumin; Disease Models, Animal; Food Hypersensitivity; Intestinal Mucosa; Intestines; Mast Cells; Mastocytosis; Mice; NF-kappa B; Ovalbumin; Phosphorylation; Signal Transduction

Aspirin (ASP)-facilitated absorption of ingested allergens is considered an exacerbating factor in the development of food allergy. Sodium cromoglycate (SCG) is used for the treatment of atopic dermatitis with food allergy, but the efficacy of SCG in ASP-exacerbated food-allergy reactions is unclear. In this study, we evaluated the effect of SCG on ASP-exacerbated food-allergic reactions, as well as allergen absorption, in egg-allergic model rats.. Plasma concentrations of ovalbumin (OVA) and fluorescein isothiocyanate-labeled dextran (FD-40), a marker for nonspecific-absorption pathways, were measured after oral administration of mixtures of OVA and FD-40 in OVA-unsensitized and OVA-sensitized rats. IgE-mediated allergic reactions were evaluated by measuring changes in rectal temperature and Evans blue dye (EBD) extravasation in the intestine and liver after oral challenge with OVA. The effects of ASP and SCG on such absorption and allergic reactions were also evaluated kinetically.. In OVA-sensitized rats, plasma concentrations of OVA and FD-40 were significantly higher than those in unsensitized rats after oral administration. ASP increased the intestinal absorption of OVA and FD-40 via the paracellular pathway, and a lower rectal temperature and higher EBD extravasation were detected in the intestine and liver of OVA-sensitized rats. SCG ameliorated these ASP-facilitated absorptions and allergic reactions in a dose-dependent manner. In particular, high-dose SCG (195.2 μmol/kg) completely inhibited these absorptions and reactions.. SCG can prevent ASP-exacerbated allergic reactions in patients with food allergy resulting from inhibition of increases in allergen absorption.

Topics: Administration, Oral; Allergens; Anaphylaxis; Animals; Aspirin; Cromolyn Sodium; Disease Models, Animal; Disease Progression; Egg Hypersensitivity; Immunization; Immunoglobulin E; Male; Ovalbumin; Rats

Turmeric (Curcuma longa) has traditionally been used to treat pain, fever, allergic and inflammatory diseases such as bronchitis, arthritis, and dermatitis. In particular, turmeric and its active component, curcumin, were effective in ameliorating immune disorders including allergies. However, the effects of turmeric and curcumin have not yet been tested on food allergies.. Mice were immunized with intraperitoneal ovalbumin (OVA) and alum. The mice were orally challenged with 50mg OVA, and treated with turmeric extract (100mg/kg), curcumin (3mg/kg or 30 mg/kg) for 16 days. Food allergy symptoms including decreased rectal temperature, diarrhea, and anaphylaxis were evaluated. In addition, cytokines, immunoglobulins, and mouse mast cell protease-1 (mMCP-1) were evaluated using ELISA.. Turmeric significantly attenuated food allergy symptoms (decreased rectal temperature and anaphylactic response) induced by OVA, but curcumin showed weak improvement. Turmeric also inhibited IgE, IgG1, and mMCP-1 levels increased by OVA. Turmeric reduced type 2 helper cell (Th2)-related cytokines and enhanced a Th1-related cytokine. Turmeric ameliorated OVA-induced food allergy by maintaining Th1/Th2 balance. Furthermore, turmeric was confirmed anti-allergic effect through promoting Th1 responses on Th2-dominant immune responses in immunized mice.. Turmeric significantly ameliorated food allergic symptoms in a mouse model of food allergy. The turmeric as an anti-allergic agent showed immune regulatory effects through maintaining Th1/Th2 immune balance, whereas curcumin appeared immune suppressive effects. Therefore, we suggest that administration of turmeric including various components may be useful to ameliorate Th2-mediated allergic disorders such as food allergy, atopic dermatitis, and asthma.

Topics: Allergens; Anaphylaxis; Animals; Chymases; Curcuma; Curcumin; Cytokines; Disease Models, Animal; Female; Food Hypersensitivity; Immunoglobulin E; Immunoglobulin G; Mice, Inbred BALB C; Ovalbumin; Phytotherapy; Plant Extracts; Th1 Cells; Th2 Cells

Anaphylaxis is a rapid-onset, life-threatening allergic reaction in that IgE, mast cells and histamine are commonly involved. It can be experimentally induced in IgE-sensitized animals by intravenous injection of corresponding allergens, and the sign of anaphylactic reaction can be detected within minutes after allergen challenge. However, it remains puzzling why the anaphylactic reaction can be initiated in vivo so quickly, considering that allergens are delivered into the blood circulation while mast cells reside within peripheral tissues but not in the blood circulation. To address this issue, we compared two different forms of the same allergen, small soluble and large particulate ones, in their ability to induce anaphylaxis in IgE-sensitized mice. In contrast to our expectation, particulate allergens could induce anaphylaxis as quickly and efficiently as did soluble allergens, even though they remained inside of blood vessels. In vivo imaging analysis suggested the direct interaction of intravascular particulate allergens and perivascular mast cells across the capillary wall. Taken together with previous report that perivascular mast cells can capture IgE in the blood circulation by extending cell processes across the vessel wall, our findings imply that blood-circulating allergens, regardless of their size, can stimulate mast cells without exit from blood vessels, by means of cross-linking IgE on mast cell processes inserted into the vessel lumen, and hence initiate anaphylactic reaction so quickly.

Topics: Allergens; Anaphylaxis; Animals; Capillaries; Immunoglobulin E; Mast Cells; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Microspheres; Ovalbumin; Particle Size; Passive Cutaneous Anaphylaxis; Polystyrenes; Solubility

Experimental IgE-mediated food allergy depends on intestinal anaphylaxis driven by interleukin-9 (IL-9). However, the primary cellular source of IL-9 and the mechanisms underlying the susceptibility to food-induced intestinal anaphylaxis remain unclear. Herein, we have reported the identification of multifunctional IL-9-producing mucosal mast cells (MMC9s) that can secrete prodigious amounts of IL-9 and IL-13 in response to IL-33, and mast cell protease-1 (MCPt-1) in response to antigen and IgE complex crosslinking, respectively. Repeated intragastric antigen challenge induced MMC9 development that required T cells, IL-4, and STAT6 transcription factor, but not IL-9 signals. Mice ablated of MMC9 induction failed to develop intestinal mastocytosis, which resulted in decreased food allergy symptoms that could be restored by adoptively transferred MMC9s. Finally, atopic patients that developed food allergy displayed increased intestinal expression of Il9- and MC-specific transcripts. Thus, the induction of MMC9s is a pivotal step to acquire the susceptibility to IgE-mediated food allergy.

Topics: Adoptive Transfer; Anaphylaxis; Animals; Base Sequence; Bone Marrow Cells; Cell Lineage; Chymases; Diarrhea; Disease Susceptibility; Duodenum; Food Hypersensitivity; Humans; Hypersensitivity, Immediate; Immunoglobulin E; Interleukin-9; Interleukins; Intestinal Mucosa; Mast Cells; Mastocytosis; Mice; Mice, Inbred Strains; Molecular Sequence Data; Ovalbumin; RNA, Messenger; Species Specificity; STAT6 Transcription Factor; T-Lymphocytes

IgE mainly activates cells via two receptors, FcɛRI and FcɛRII. Blocking antibodies against and animals genetically targeted for these receptors have been successfully used to distinguish between these two activating pathways. In the present study, we investigated whether our newly established anti-ovalbumin (OVA) monoclonal IgE OE-2 induced FcɛRII-dependent activation, but not FcɛRI-dependent activation in vivo and in vitro, in contrast to the previously established anti-OVA IgE OE-1, which stimulated FcɛRI and FcɛRII. The FcɛRI-mediated degranulation of RBL2H3 cells and passive systemic anaphylaxis in mice were induced by OE-1 but not OE-2. On the other hand, the production of nitric oxide by rat peritoneal macrophages and the primary antibody response in mice against co-injected OVA, which were mediated through FcɛRII, were induced and enhanced by OE-1 and OE-2. Differences in the epitopes recognized by OE-1 and OE-2 may partially explain why OE-1, but not OE-2, triggered FcɛRI-dependent activation. OE-1 bridged FcɛRI through effective aggregation with OVA, whereas OE-2 crosslinked the receptor strongly and only moderately upon the addition of an anti-kappa antibody and polymerized OVA, namely, an OVA-conjugated resin, respectively, resulting in degranulation. Our results offer a novel approach for determining the relative importance of FcɛRI and FcɛRII in various IgE-dependent responses by using OE-1 and OE-2.

Topics: Anaphylaxis; Animals; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal; Antibody Specificity; Cell Degranulation; Cell Line; Epitopes; Gene Expression; Immunoglobulin E; Macrophages, Peritoneal; Male; Mast Cells; Mice; Mice, Inbred DBA; Nitric Oxide; Ovalbumin; Protein Aggregates; Protein Binding; Rats; Receptors, IgE

Recent research indicates that injections inducing unwanted anaphylactoid reactions occur frequently in a clinical setting. In this paper, we explored anaphylactoid reactions trends in animal models following ginsenosides injections.. Our anaphylactoid animal model was optimized by comparing reactions between BN rats, SD rats, guinea pigs and ICR mice to first intravenous exposure to standard compounds including ovalbumin (OVA), tannic acid (TA), Tween 80 (T80), bovine serum albumin (BSA) and Compound 48/80 (C48/80), Shengmai injection (SMI) and Xuesaitong injection (XSTI) which contains ginsenosides, respectively. The anaphylactoid symptoms were documented and the plasma levels of histamine were assessed. Subsequently, the IgE levels and total complement activity (CH50) were determined to further explore the mechanisms underlying the observed anaphylactoid reactions on the optimized animal model.. We observed that BN rats and guinea pigs exhibited particularly exacerbated symptoms after administration of OVA, T80, TA, SMI and XSTI. Regarding histamine levels, we observed that BN rats were more sensitive to TA and XSTI, guinea pigs were more sensitive to OVA, T80 and SMI, and SD rats were more sensitive to C48/80. According to both anaphylactoid symptom scores and histamine secretion rates, BN rats, in particular, were found to be more sensitive to OVA, T80, TA, SMI and XSTI. Noteworthy however, the four rodents showed significantly weaker anaphylactoid reactions after administration of BSA.. BN rats were more suitable for comprehensive evaluation of anaphylatoid reactions following injections; both IgE levels and CH50 could be used as auxiliary mediators for the assessment of anaphylactoid reactions.

Topics: Anaphylaxis; Animals; Disease Models, Animal; Guinea Pigs; Immunoglobulin E; Injections; Male; Mice; Mice, Inbred ICR; Ovalbumin; Rats; Rats, Inbred BN; Rats, Sprague-Dawley

Almost a quarter of the world population suffers from IgE-mediated allergies. T cells and IgG-producing B cells can produce protection, but treatment for disease is laborious with unsatisfactory patient compliance.. We sought to identify whether paediatric allergy vaccines affected later allergen sensitization and onset of disease when used prophylactically.. A murine model of anaphylaxis was applied. Mice were first immunized with monovalent or multivalent allergy vaccines that also contained aluminium hydroxide and CpG oligodeoxynucleotide as adjuvants. Later, the mice were sensitized by multiple low-dose injections of aluminium-adsorbed allergen. After a dormant period, the mice were challenged systemically with high-dose allergen, and the clinical signs of anaphylaxis were recorded. Throughout the immunization and sensitization periods, blood was collected for serological testing.. Immunization with allergy vaccines produced antigen-specific protection against sensitization as measured by systemic anaphylaxis in mice. The long-term effect was observed both after juvenile (5-6 weeks) and neonatal (7 days) vaccination. Monovalent and pentavalent vaccines were protective to a similar level. Protection was associated with increased secretion of IgG2a and production of IFN-γ. Protection could also be transferred to sensitized mice via serum or via CD25-positive CD4 T cells.. Prophylactic and multivalent allergy vaccines in juvenile and neonatal mice protected against later sensitization and anaphylaxis. Such treatment may provide a rational measure for future management of allergen-related diseases and their strong socio-economic impact on daily life.

Topics: Adoptive Transfer; Allergens; Anaphylaxis; Animals; Cross Protection; Disease Models, Animal; Female; Humans; Immunization Schedule; Immunoglobulin E; Immunoglobulin G; Mice; Ovalbumin; Rhinitis, Allergic; Rhinitis, Allergic, Perennial; Vaccines

Administration of the influenza vaccination to patients with an egg allergy is major health concern. Contaminating egg antigens occasionally induce severe anaphylactic shock in these patients following administration of the vaccination; therefore, the development of a safer vaccination is needed. In the present study, we investigated whether a mixture of four newly and previously generated anti-ovalbumin (OVA) IgA monoclonal antibodies (mAbs) could inhibit both anaphylactic shock upon a subcutaneous OVA challenge and subsequent further sensitization against OVA in passively anti-OVA IgE-sensitized mice and actively sensitized mice with an injection of OVA. The prevention of anaphylaxis by anti-OVA IgA mAbs was suggested to be mediated through the inhibition of OVA binding to allergenic antibodies such as anti-OVA IgE on mast cells and deceleration of the rate of OVA penetration from the injected site into the systemic circulation. Anti-OVA IgA mAbs inhibited further sensitization against OVA in mice actively sensitized with OVA, but did not affect sensitization against the unrelated antigen, phosphorylcholine-keyhole limpet hemocyanin co-injected with OVA. Our findings indicate that adding the anti-egg antigen IgA to the influenza vaccine should reduce not only the risk of inducing anaphylactic shock, but also undesired further sensitization against egg antigens following the vaccination without affecting the intended beneficial effect of the vaccine, namely the upregulation of immune responses to influenza viruses.

Topics: Anaphylaxis; Animals; Antibodies, Monoclonal; Disease Models, Animal; Humans; Influenza Vaccines; Male; Mice; Mice, Inbred DBA; Ovalbumin; Statistics, Nonparametric

Aqueous extract of Qu Feng Xuan Bi Formula (QFXBF, a Chinese herb formula) which composed of Radix Glycyrrhizae, Radix Glycyrrhizae Preparata, Paeonia sterniana Fletcher in Journ, Pheretima, Allium macrostemon Bunge, Astragalus membranaceus (Fisch) Bunge and Divaricate Saposhnikovia Root has been used in treatment of allergic rhinitis and asthma (ARA) as an approved hospital prescription for many years in Jiangsu Province Hospital of Traditional Chinese Medicine, China. The present study was designed to investigate the effect of the aqueous extract of QFXBF in the gene expression of Toll-like receptor 9 (TLR9) and the manners of immune modulation of T cell-associated interleukin (IL-4 and IL-13) in rat ARA models.. Fifty SD male rats were divided into five groups: not treated group, OVA only group (treated only with OVA), dexamethasone (DXM) group, low dose QFXBF group and high dose QFXBF group randomly (n=10 per group). Rat allergic rhinitis and asthma model was developed by ovalbumin (OVA) sensitization and nose infusion. Pathological changes of nasal tissue and lungs were examined by H&E staining. Gene expressions of TLR9, Stat 3, Jak-1 and C-Jun in nasal tissue were assayed by real-time polymerase chain reaction (RT-PCR). The serum and broncho-alveolar lavage fluid (BALF) levels of T cell-associated interleukin (IL-4 and IL-13) were determined by enzyme-linked immunosorbent assay (ELISA).. The ARA model was successfully established. Marked EOS count was observed in BALF from ARA models. The aqueous extract of QFXBF could reduce EOS levels and increase TLR9 expression, but did not affect the gene expression of Stat-3 and Jak-1 and C-Jun. The reduction of IL-13 concentration in serum from high dose QFXBF group was observed in BALF, albeit not significantly. Despite the not treated group, serum levels of IL-4 had significantly increased in other four groups (P<0.001, n=4-6) but made higher in low dose QFXBF group and DXM group (P<0.05, n=4-6).. This study originally provides the evidence that the aqueous extract of Qu Feng Xuan Bi Formula alone is effective in the treatment of anaphylactic rhinitis-asthma symptoms. The extract of Qu Feng Xuan Bi Formula was effective to reduce the eosophil recruitment to the lung. In addition it increased the IL-4 concentration in the BALF and expression of TLR9 in the nasal tissue. No alteration was observed in the IL-13 concentration in the BALF and expression of STAT-3, JAK-1 and C-Jun in nasal tissue. The results thereby scientifically provided mechanism of these aqueous extract of QFXBF in improvement of ARA and supported its clinical use.

Topics: Anaphylaxis; Animals; Asthma; Bronchoalveolar Lavage Fluid; Dexamethasone; Drugs, Chinese Herbal; Eosinophils; Gene Expression Regulation; Interleukin-13; Interleukin-4; Male; Ovalbumin; Plant Extracts; Rats; Rats, Sprague-Dawley; Real-Time Polymerase Chain Reaction; Rhinitis; T-Lymphocytes; Toll-Like Receptor 9

Food allergy, which accompanies acute symptoms such as pruritus, vomiting, diarrhea, and lethal anaphylactic shock is an increasing clinical problem. Skullcap (Scutellaria baicalensis Georgi) has been widely used as a traditional herbal medicine to treat inflammation, cancer, and allergy, but its effects in treating food allergy are not yet known.. To examine the effect of skullcap on food allergy, female BALB/c mice were sensitized with 20 μg OVA and 2mg alum by intraperitoneal injection on day 0. From day 17, mice were orally challenged with OVA (50 mg) in saline every 3 days, for a total of six times. To investigate the preventive effect, skullcap (25 mg/kg) was orally administered every day from day 17 to 34.. Food allergy symptoms were evaluated by the criteria for diarrhea, anaphylactic response, and rectal temperature. Severe symptoms of food allergy were observed in the sham group (diarrhea, 3 points; anaphylactic response, 2.6 points; rectal temperature, -8.36 °C. In contrast, the skullcap treatment group had a significantly suppressed OVA-induced anaphylactic response (1.3 points) and rectal temperature (-4.76°C). Moreover, both OVA-specific IgE, Th17 cytokine (IL-17), and Th2-related cytokines (IL-4, IL-5, IL-10, and IL-13), which increased with food allergy, were significantly inhibited by skullcap treatment.. We demonstrate that the administration of skullcap attenuates OVA-induced food allergy symptoms through regulating systemic immune responses of Th cells. These results indicate that skullcap may be a potential candidate as a preventive agent for food allergy.

Topics: Allergens; Anaphylaxis; Animals; Anti-Allergic Agents; Body Temperature; Cytokines; Diarrhea; Disease Models, Animal; Female; Food Hypersensitivity; Immunoglobulin E; Immunoglobulin G; Mice, Inbred BALB C; Ovalbumin; Phytotherapy; Plant Extracts; Scutellaria baicalensis; Spleen

Cutaneous sensitization with a food antigen before its consumption elicits the development of food allergy. Here, we report the site- and stage-dependent roles of basophils and proallergic cytokines, thymic stromal lymphopoietin (TSLP) and IL-33, in a mouse model of food allergy initially sensitized cutaneously with the food antigen. Mice were epicutaneously sensitized with the food antigen ovalbumin (OVA) followed by oral challenge with OVA. Epicutaneously sensitized mice produced OVA-specific IgE and developed IgE-dependent anaphylaxis after oral challenge. Basophil-depleted or TSLP-receptor-deficient mice did not produce OVA-specific IgE and were protected from oral challenge-induced anaphylaxis. IL-33-deficient mice produced normal levels of OVA-specific IgE. However, IL-33-deficient mice and mice treated with recombinant soluble IL-33 receptor were protected from anaphylaxis. Thus, basophils and TSLP have pivotal roles in Th2 development in the skin during the sensitization phase of food allergy. In contrast, while IL-33 is dispensable for promoting cutaneous antigen sensitization, the cytokine is essential for inducing IgE-dependent anaphylaxis in the gut.

Topics: Allergens; Anaphylaxis; Animals; Basophils; Cytokines; Disease Models, Animal; Female; Food Hypersensitivity; Immunoglobulin E; Interleukin-33; Interleukins; Mice; Mice, Knockout; Ovalbumin; Skin; Th2 Cells; Thymic Stromal Lymphopoietin

Serum IgG, IgE and IgM have been shown to enhance the primary antibody responses upon exposure to the soluble antigens recognized by those antibodies. However, how IgA affects these responses remains unknown.. We investigated the effects of intravenously administered monoclonal IgA on the immune responses in mice.. DBA/1J mice were immunized with ovalbumin in the presence or absence of anti-ovalbumin monoclonal IgA. The Th1 and Th2 immune responses to ovalbumin and the anaphylaxis induced by re-exposure to ovalbumin were measured.. IgA complexed with antigen attenuated the primary antibody responses to the antigen in mice, in contrast to IgG2b and IgE. The primary antibody responses, i.e. the de novo synthesis of anti-ovalbumin IgG2a, IgG1 and IgE in the serum, and the subsequent anaphylaxis induced with re-exposure to ovalbumin were reduced by the co-injection of anti-ovalbumin monoclonal IgA at ovalbumin immunization. The Th1, Th2 and Tr1 cytokines interferon-γ, interleukin-4 and interleukin-10, respectively, released from ovalbumin-restimulated cultured splenocytes collected from allergic mice were also reduced by the treatment. The induction of interferon-γ and interleukin-4 secretion by splenocytes from ovalbumin-immunized mice stimulated in vitro with ovalbumin was also significantly reduced by the antigen complexed with anti-ovalbumin IgA.. These data suggest that the direct inhibition of Th1 and Th2 activation by anti-ovalbumin monoclonal IgA participates in the inhibition of the primary antibody responses. IgA plays important immunosuppressive roles under physiological and pathological conditions and is a promising candidate drug for the treatment of immune disorders.

Topics: Anaphylaxis; Animals; Antibody Formation; Antigen-Antibody Complex; Cells, Cultured; Epitopes; Female; Immunoglobulin A; Immunoglobulins, Intravenous; Lymphocyte Activation; Mice; Mice, Inbred DBA; Ovalbumin; Th1 Cells; Th2 Cells

The prevalence of food allergy is rising in the western world. Allergen restriction is the chosen treatment in this condition, but continuous ingestion of the antigen has shown positive results in clinical trials. In a previous study, we have shown several allergic and metabolic alterations after 7 days of ovalbumin (OVA) ingestion by sensitized mice. The aim of this study was to investigate whether prolonged ingestion of antigen by sensitized mice would reverse the metabolic consequences caused by experimental food allergy. For this, allergic and metabolic parameters were analysed after prolonged ingestion of an OVA diet by OVA-sensitized mice. As shown previously, after 7 days of OVA consumption, sensitized mice showed increased serum levels of anti-OVA immunoglobulin (Ig)E and IgG1, aversion to the antigen ingestion, marked body and adipose tissue weight loss, followed by adipose tissue inflammation and decreased serum levels of adipokines, glucose and triglycerides. However, after 14 days of oral challenge, sensitized mice showed an anti-OVA IgE level similar to the mice that were only sensitized, but the specific IgG1 did not change. With this prolonged ingestion of OVA, sensitized mice were protected from OVA-induced anaphylaxis when the antigen was given systemically at a dose of 2 mg/animal. Moreover, various parameters analysed were significantly ameliorated, including adipose tissue inflammation, body and adipose tissue loss, as well as serum levels of adipokines and triglycerides. Therefore, our data suggest that prolonged ingestion of OVA by sensitized mice results in an improvement of the metabolic consequences caused by experimental food allergy.

Topics: Adipose Tissue; Anaphylaxis; Animal Feed; Animals; Food Hypersensitivity; Glucose; Immunization; Immunoglobulin E; Male; Mice; Mice, Inbred BALB C; Ovalbumin; Weight Loss

MicroRNAs (miRNAs) are small, noncoding RNAs that have been shown to play a critical role in normal physiology and disease, such as hematopoietic development and cancer. However, their role in mast-cell function and development is poorly understood. The major objective of this study was to determine how global miRNA expression affects mast-cell physiology. The RNase III endonuclease, Dicer, is required for the processing of pre-miRNAs into mature miRNAs. To investigate the effect of global miRNA depletion on mast cells in vivo, we generated a mast-cell-specific knock out of Dicer in mice. Transgenic mice (Mcpt5-Cre) that express Cre selectively in connective tissue mast cells were crossed with mice carrying the floxed conditional Dicer allele (Dicer fl/fl). Mcpt5-Cre × Dicer fl/fl mice with homozygous Dicer gene deletion in mast cells were found to have a profound mast-cell deficiency with near complete loss of peritoneal, gastrointestinal, and skin mast cells. We examined the in vivo functional consequence of mast-cell-specific Dicer deletion using an immunoglobulin-E-dependent passive systemic anaphylaxis murine model. Immunoglobulin-E-sensitized wild type Mcpt5-Cre × Dicer +/+ and heterozygous Mcpt5-Cre × Dicer fl/+ mice show marked hypothermia with antigen; however, homozygous Mcpt5-Cre × Dicer fl/fl mice were completely unresponsive to antigen challenge. These studies suggest a critical role for Dicer and miRNA expression for establishment of tissue compartments of functional mast cells in vivo.

Topics: Anaphylaxis; Animals; Cell Count; Crosses, Genetic; DEAD-box RNA Helicases; Gene Expression Regulation; Genotype; Humans; Hypothermia; Immunization; Mast Cells; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; MicroRNAs; Organ Specificity; Ovalbumin; Peritoneum; Ribonuclease III; Serum Albumin; Skin; Stomach

Systemic anaphylaxis is life-threatening, and its pathophysiology is not fully clarified. Mice are frequently used for experimental study on anaphylaxis. However, the hemodynamic features and mechanisms of mouse anaphylactic hypotension remain unknown. Therefore, we determined mechanisms of systemic and pulmonary vascular response to anaphylactic hypotension in anesthetized BALB/c mice by using receptor antagonists of chemical mediators.. Anaphylaxis was actively induced by an intravenous injection of the ovalbumin antigen into open-chest artificially ventilated sensitized mice. Mean arterial pressure (MAP), pulmonary arterial pressure (PAP), left atrial pressure, central venous pressure, and aortic blood flow (ABF) were continuously measured.. In sensitized control mice, MAP and ABF showed initial, transient increases, followed by progressive decreases after the antigen injection. Total peripheral resistance (TPR) did not decrease, while PAP initially and transiently increased to 18.5±0.5mmHg and pulmonary vascular resistance (PVR) also significantly increased. The antigen-induced decreases in MAP and ABF were attenuated by pretreatment with either a platelet-activating factor (PAF) receptor antagonist, CV6209, or a histamine H1 receptor antagonist, diphenhydramine, and were abolished by their combination. Diphenhydramine augmented the initial increases in PAP and PVR, but did not affect the decrease of the corresponding MAP fall. The antagonists of either leukotriene C4 or serotonin, alone or in combination with CV6209, exerted no significant effects.. Mouse anaphylactic hypotension is caused by a decrease in cardiac output but not vasodilatation, via actions of PAF and histamine. The slight increase in PAP is not involved in mouse anaphylactic hypotension.

Topics: Anaphylaxis; Animals; Arterial Pressure; Cardiac Output; Diphenhydramine; Hemodynamics; Histamine; Hypotension; Male; Mice; Mice, Inbred BALB C; Ovalbumin; Platelet Activating Factor; Platelet Membrane Glycoproteins; Pyridinium Compounds; Receptors, G-Protein-Coupled; Vascular Resistance; Vasoconstriction; Vasodilation

Allergic responses are the result of the activation of mast cells and basophils, and the subsequent release of vasoactive and proinflammatory mediators. Exposure to an allergen in a sensitized individual can result in clinical symptoms that vary from minor erythema to life threatening anaphylaxis. In the laboratory, various animal models have been developed to understand the mechanisms driving allergic responses. Herein, we describe a detailed method for measuring changes in vascular permeability to quantify localized allergic responses. The local anaphylaxis assay was first reported in the 1920s, and has been adapted from the technique published by Kojima et al. in 2007(1). In this assay, mice sensitized to OVA are challenged in the left ear with vehicle and in the right ear with OVA. This is followed by an intravenous injection of Evans Blue dye. Ten min after injecting Evans Blue, the animal is euthanized and the dye that has extravasated into the ears is extracted overnight in formamide. The absorbance of the extracted dye is then quantified with a spectrophotometer. This method reliably results in a visual and quantifiable manifestation of a local allergic response.

Topics: Anaphylaxis; Animals; Capillary Permeability; Evans Blue; Histamine Release; Immunoglobulin E; Mast Cells; Mice; Mice, Inbred BALB C; Ovalbumin

Immunoglobulin E (IgE) production is tightly regulated at the cellular and genetic levels and is believed to be central to allergy development. At least two cellular pathways exist that lead to systemic anaphylaxis reactions in vivo: IgE-sensitized mast cells and IgG1-sensitized basophils. Passive anaphylaxis, by application of allergen and allergen-specific antibodies in mice, indicates a differential contribution of immunoglobulin isotypes to anaphylaxis. However, analysis of a dynamic immunization-mediated antibody response in anaphylaxis is difficult. Here, we generated IgE knock-in mice (IgE(ki) ), which express the IgE heavy chain instead of IgG1, in order to analyze the contribution of IgG1 and IgE to active anaphylaxis in vivo. IgE(ki) mice display increased IgE production both in vitro and in vivo. The sensitization of IgE(ki) mice by immunization followed by antigen challenge leads to increased anaphylaxis. Homozygous IgE(ki) mice, which lack IgG1 due to the knock-in strategy, are most susceptible to active systemic anaphylaxis. The depletion of basophils demonstrates their importance in IgE-mediated anaphylaxis. Therefore, we propose that an enhanced, antigen-specific, polyclonal IgE response, as is the case in allergic patients, is probably the most efficient way to sensitize basophils to contribute to systemic anaphylaxis in vivo.

Topics: Allergens; Anaphylaxis; Animals; Antibodies, Monoclonal; Basophils; Gene Knock-In Techniques; Homozygote; Humans; Immunization; Immunoglobulin E; Immunoglobulin G; Mast Cells; Mice; Ovalbumin; Severity of Illness Index

Chaga mushrooms (Inonotus obliquus) are hypothesised to exhibit general immune-potentiating, anti-inflammatory, and antitumor properties, but their anti-allergic activities are not fully understood. Therefore, this study investigated whether a chaga mushroom extract (C-HE) might have anti-allergic activity. This activity was assessed through the levels of the IgE Ab produced in response to an allergen (OVA). The administration of C-HE prophylactically inhibited the systemic anaphylactic shock induced by compound 48/80 in mice. The oral administration of C-HE significantly reduced the total IgE levels in mice and slightly affected the production of IgG1. Furthermore, spleen cell cultures harvested from OVA-sensitised mice that had received C-HE orally showed a significant increase in Th1-derived responses (IFN-γ production). Therefore, our results suggest that the chaga mushroom extract may be used as an anti-allergic functional food.

Topics: Anaphylaxis; Animals; Anti-Allergic Agents; Basidiomycota; Cells, Cultured; Female; Immunoglobulin E; Interferon-gamma; Mice; Mice, Inbred BALB C; Ovalbumin; p-Methoxy-N-methylphenethylamine; Spleen; Th1 Cells

Herbal medicines have ever been thought harmless, but it is obviously not true. Many adverse reports emerged with the development of their popular application in the world. Allergic reactions, especially serious immediate hypersensitivity, frequently occurred when herbal injections were used in clinic and made this ever prevailing agent nearly disappear in China. The aim of this study is to establish a rapid and economical method for the prediction of the allergenicity of herbal injections. Ovalbumin (OVA) and four other herbal injections, in which two of them were well known for their allergenicity, were selected to sensitize and stimulate the animals. Serotonin in the animal serum was detected with HPLC to reflect the anaphylactic response and compared with the other cytokines which could mediate the anaphylaxis, including histamine, IgE and β-hexosaminidase. The results suggest that serotonin can be detected quickly and has good correlation with the other allergy-related cytokines. It is a promising way for predicting the allergenicity of the herbal injections and those complicated natural products.

Topics: Allergens; Anaphylaxis; Animals; beta-N-Acetylhexosaminidases; China; Chromatography, High Pressure Liquid; Cytokines; Drugs, Chinese Herbal; Guinea Pigs; Histamine; Hypersensitivity, Immediate; Immunoglobulin E; Injections; Male; Ovalbumin; Serotonin

Hepatic venoconstriction occurs in rat anaphylactic hypotension. However, the exact venoconstrictive site remains unknown, and we therefore attempted to determine its location by using hepatic venography and histology. Anaphylaxis was induced in anesthetized Sprague-Dawley rats by i.v. administration of ovalbumin antigen. Venography of the portal vein (n = 8) was obtained at baseline and maximal hepatic venoconstriction. We separately examined photomicrographs of the liver sections. Along with systemic hypotension, portal venous pressure increased to a peak of 28 ± 3 cm- H2O at 2 min after antigen injection. Post-antigen portal venography revealed that 40% of portal venuls (76 vessels/total 188 vessels) with diameters from 160 to 300 μm were not visualized, suggesting that stenosis or obliteration occurred distally. The corresponding upstream portal vessels exhibited markedly bulging. Stenosis was also observed in some portal branches with diameters from 180 to 420 μm (9%; 17 vessels/total 188 vessels). Light microscopically, most portal venules with an estimated baseline diameter less than 110 μm showed stenosis, but statistically significant stenosis was found in those with baseline diameters of 20-70 μm. In conclusion, anaphylactic hepatic venoconstriction occurs over a wide range of portal veins with diameters less than 420 μm, and occurs markedly in portal venules with diameters less than 70 μm in anesthetized rats.

Topics: Anaphylaxis; Anesthesia; Animals; Constriction, Pathologic; Liver; Male; Ovalbumin; Phlebography; Portal Vein; Rats

Rapid desensitization transiently prevents severe allergic reactions, allowing administration of life-saving therapies in previously sensitized patients. However, the mechanisms underlying successful rapid desensitization are not fully understood.. We sought to investigate whether the mast cell (MC) is an important target of rapid desensitization in mice sensitized to exhibit IgE-dependent passive systemic anaphylaxis in vivo and to investigate the antigen specificity and underlying mechanisms of rapid desensitization in our mouse model.. C57BL/6 mice (in vivo) or primary isolated C57BL/6 mouse peritoneal mast cells (PMCs; in vitro) were passively sensitized with antigen-specific anti-2,4-dinitrophenyl IgE, anti-ovalbumin IgE, or both. MCs were exposed over a short period of time to increasing amounts of antigen (2,4-dinitrophenyl-human serum albumin or ovalbumin) in the presence of extracellular calcium in vitro or by means of intravenous administration to sensitized mice in vivo before challenging the mice with or exposing the PMCs to optimal amounts of specific or irrelevant antigen.. Rapidly exposing mice or PMCs to progressively increasing amounts of specific antigen inhibited the development of antigen-induced hypothermia in sensitized mice in vivo and inhibited antigen-induced PMC degranulation and prostaglandin D2 synthesis in vitro. Such MC hyporesponsiveness was induced antigen-specifically and was associated with a significant reduction in antigen-specific IgE levels on MC surfaces.. Rapidly exposing MCs to progressively increasing amounts of antigen can both enhance the internalization of antigen-specific IgE on the MC surface and also desensitize these cells in an antigen-specific manner in vivo and in vitro.

Topics: 2,4-Dinitrophenol; Anaphylaxis; Animals; Antibodies, Anti-Idiotypic; Antibody Specificity; Antigens; Desensitization, Immunologic; Humans; Hypersensitivity; Immunoglobulin E; Mast Cells; Mice; Mice, Inbred C57BL; Ovalbumin; Time Factors

Vaccine administration into the intestine is known to induce mucosal tolerance most efficiently. Therefore, developing a delivery system that targets the intestinal mucosa is expected to improve the efficiency of immunosuppression. Human enteric adenovirus serotype 40 (Ad40)-based vectors have the advantage of targeting intestinal mucosa, making them prime candidates as mucosal vaccine carriers for immunosuppression. Here, after both oral and intraduodenal administrations, the vector distribution of replication-defective recombinant Ad40 vectors (rAd40) was significantly higher than that of a conventional Ad vector based on human adenovirus 5 (Ad5) in ilea containing Peyer's patches. Single intraduodenal administration of rAd40 induced antigen-specific mucosal immunoreaction mediated by intestinal mucosal and systemic immunity. In ovalbumin-induced allergy mouse models, this approach inhibited antigen-specific delayed-type hypersensitivity reactions, diarrhea occurrence, and systemic anaphylaxis. Thus, a single intraduodenal administration of rAd40 provides a potent method of inducing allergen-specific mucosal tolerance and a new allergen-specific immunotherapy for overcoming problems with current therapies against life-threatening allergic reactions, including anaphylaxis.

Topics: Adenovirus Vaccines; Adenoviruses, Human; Allergens; Anaphylaxis; Animals; Duodenum; Female; Immune Tolerance; Intestinal Mucosa; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Ovalbumin

Anaphylaxis is a severe, potentially life-threatening reaction that can occur in response to common triggers, including food allergens (e.g., peanut), insect stings, and several medications. Activation of mast cells and basophils to release preformed mediators, such as histamine, is thought to be an important process that underlies reactions. Histamine can exert effects through four different receptors, termed H1R-H4R. Despite clinical use of both H1R and H2R blockers in the therapy for acute allergic reactions, there is little mechanistic evidence to support the necessity for blocking H2R, a receptor best characterized for its role in stomach acid production.. Here, we sought to define the necessity for histamine receptors in the pathology of anaphylaxis using H1R and H2R knockout (KO) mice, as well as a H1R/H2R double KO strain.. In response to IgE-mediated systemic anaphylaxis, the symptoms and decreases in core body temperature observed in wild-type mice were reduced but not ablated in either H1R or H2R KO. In contrast, H1R/H2R KO were significantly protected and were indistinguishable from histamine-deficient mice. Intravenous injection of histamine was sufficient to elicit these responses, and similar to IgE-mediated anaphylaxis, loss of both H1R and H2R was necessary for complete protection.. Our data demonstrate definitively that both H1R and H2R participate in the immediate systemic responses during histamine-associated pathophysiology and mechanistically support the utility of H2R-blocking therapeutics in alleviating symptoms of anaphylaxis.

Topics: Anaphylaxis; Animals; Antibody Specificity; Disease Models, Animal; Histamine; Immunoglobulin E; Mice; Mice, Knockout; Ovalbumin; Receptors, Histamine H1; Receptors, Histamine H2

Stimulatory IgG receptors (FcγRs) on bone marrow-derived cells contribute to the pathogenesis of several autoimmune and inflammatory disorders. Monoclonal antibodies that block FcγRs might suppress these diseases, but they can induce anaphylaxis.. We wanted to determine whether a rapid desensitization approach can safely suppress IgG/FcγR-mediated anaphylaxis.. Mice were injected with serially increasing doses of 2.4G2, a rat mAb that blocks the inhibitory FcγR, FcγRIIb, and the stimulatory receptor, FcγRIII. Rectal temperature was used to detect the development of anaphylaxis. Passive and active IgG-mediated anaphylaxis were evaluated in mice that had been rapidly desensitized with 2.4G2 or mock-desensitized in mice in which monocyte/macrophages, basophils, or neutrophils had been depleted or desensitized and in mice in which FcγRI, FcγRIII, and/or FcγRIV had been deleted or blocked.. Rapid desensitization with 2.4G2 prevented 2.4G2-induced shock and completely suppressed IgG-mediated anaphylaxis. Rapid desensitization of ovalbumin-sensitized mice with 2.4G2 was safer and more effective than rapid desensitization with ovalbumin. 2.4G2 treatment completely blocked FcγRIII and removed most FcγRI and FcγRIV from nucleated peripheral blood cells. Because IgG(2a)-mediated anaphylaxis was partially FcγRI and FcγRIV dependent, the effects of 2.4G2 on FcγRI and FcγRIV were probably crucial for its complete inhibition of IgG(2a)-mediated anaphylaxis. IgG(2a)-mediated anaphylaxis was partially inhibited by depletion or desensitization of monocyte/macrophages, basophils, or neutrophils.. IgG-mediated anaphylaxis can be induced by ligation of FcγRI, FcγRIII, or FcγRIV on monocycte/macrophages, basophils, or neutrophils and can be safely suppressed by rapid desensitization with anti-FcγRII/RIII mAb. A similar approach may safely suppress other FcγR-dependent immunopathology.

Topics: Anaphylaxis; Animals; Antibodies, Blocking; Antibodies, Monoclonal; Basophils; Body Temperature; Desensitization, Immunologic; Disease Models, Animal; Female; Hypersensitivity; Macrophages; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Neutrophils; Ovalbumin; Rats; Receptors, IgG

Venoms consist of toxic components that are delivered to their victims via bites or stings. Venoms also represent a major class of allergens in humans. Phospholipase A2 (PLA2) is a conserved component of venoms from multiple species and is the major allergen in bee venom. Here we examined how bee venom PLA2 is sensed by the innate immune system and induces a type 2 immune response in mice. We found that bee venom PLA2 induced a T helper type 2 (Th2) cell-type response and group 2 innate lymphoid cell activation via the enzymatic cleavage of membrane phospholipids and release of interleukin-33. Furthermore, we showed that the IgE response to PLA2 could protect mice from future challenge with a near-lethal dose of PLA2. These data suggest that the innate immune system can detect the activity of a conserved component of venoms and induce a protective immune response against a venom toxin.

Topics: Anaphylaxis; Animals; Bee Venoms; Crotalid Venoms; Genes, Reporter; Immunity, Innate; Immunoglobulin E; Immunoglobulin G; Insect Proteins; Interleukin-1 Receptor-Like 1 Protein; Interleukin-33; Interleukin-4; Interleukins; Lymphocyte Activation; Lysophospholipids; Melitten; Membrane Lipids; Mice; Mice, Inbred BALB C; Mice, Knockout; Myeloid Differentiation Factor 88; Ovalbumin; Phospholipases A2; Phospholipids; Receptors, IgE; Receptors, Interleukin; Th2 Cells

To clarify the relationship between selenium supplementation and type I allergic reaction, we investigated the effect of seleno-L-methionine (SeMet) supplementation on the active cutaneous anaphylaxis (ACA) reaction and cytokine production in splenocytes. Female BALB/c mice were sensitized by intraperitoneal injection of ovalbumin (OVA), and SeMet was administered orally for 2 weeks followed by a challenge with OVA to induce an ACA reaction. SeMet supplementation suppressed the ACA reaction in a dose-dependent manner. Plasma OVA-specific immunoglobulin E (IgE) level was strongly inhibited in SeMet-supplemented mice compared with control mice. The mRNA expression levels of the T helper 2 (Th2) cytokines interleukin (IL)-4 and IL-13 in the spleen of SeMet-supplemented mice were lower than those in control mice. The mRNA expression level of a Th1 cytokine, interferon (IFN)-γ, in the spleen of SeMet-supplemented mice was higher than that in control mice. Splenocytes restimulated with OVA in vitro from SeMet-supplemented mice produced lower amounts of IL-4 and IL-13 than those of control mice and higher amounts of IFN-γ than those from the control mice. These results suggest that oral SeMet supplementation suppresses OVA-induced ACA reaction by lowered Th2 cytokine production and augmenting Th1 cytokine production.

Topics: Anaphylaxis; Animals; Cytokines; Disease Models, Animal; Female; Hypersensitivity; Immunoglobulin E; Liver; Mice; Mice, Inbred BALB C; Ovalbumin; RNA, Messenger; Selenomethionine; Skin Tests; Spleen

Allergens can induce anaphylactic shock and death due to serve hypotension. Potassium channel blockers (K(+)(ATP)) such as glyburide (GLY) induce vasoconstriction. The effect of (K(+)(ATP)) channel blockers on anaphylactic shock is poorly understood. Objective of the study was to test the hypothesis that GLY reduces hypotension induced in anaphylactic shock and increases survival. Rats were grouped into: G1-N=Naïve; G2-SC=Sensitized-Control; G3-SG=Sensitized-GLY (glyburide 40 mg/kg); G4-SE=Sensitized-EPI (epinephrine 10 mg/kg). G2 to G4 groups were sensitized with ovalbumin (OVA) and shock was induced by i.v. injection of OVA. Treatments were administered intravenously 5 min later. Mean arterial pressure (MAP), heart rate (HR), and mean survival time (MST) were measured for 60 min following OVA injection and treatments administration. At the end of the experiment, blood withdrawal was performed to measure plasma levels of histamine, leukotriene B(4) (LTB(4)), prostaglandin E(2) (PGE(2)) and prostaglandin F(2) (PGF(2)). Additionally blood gas (paO2, paCO2, SaO2) and electrolytes (Na(+), K(+) and Ca (++)) were measured. MAP was normal in G1-N; severe hypotension, negative inotropic and short MST were observed in G2-SC; normalization of MAP, with lesser negative inotropism and increased MST were observed in G3-SG; full recovery was observed in G4-SE. Histamine level was significantly higher in G2-SC; reduced in G3-SG and G4-SE. PGE(2) increased in G3-SG; PGF(2) increased in G2-SC and G3-SG. Na(+) and Ca (++) concentration decreased in sensitized rats but reversed in treated groups, without change in K(+) concentration. In conclusion, our data suggest that administration of GLY reduced hypotension and increases survival time in rat anaphylactic shock.

Topics: Allergens; Anaphylaxis; Animals; Arterial Pressure; Dinoprost; Dinoprostone; Glyburide; Heart Rate; Histamine; Hypotension; Leukotriene B4; Male; Ovalbumin; Potassium Channel Blockers; Rats; Rats, Wistar

With the broad and increasing application of therapeutic monoclonal antibodies (mAbs) in clinical settings, IgG-induced allergic reactions, including passive systemic anaphylaxis (PSA), have attracted significant attention. However, it is not clear which types of IgG mAb-antigen complexes or IgG aggregates formed by antigen binding can trigger PSA, as not all immune complexes (ICs) are capable of triggering PSA. Here, we characterise mAb-antigen complexes capable of inducing murine PSA to evaluate and predict which ICs are able to induce PSA.. Thirty-six combinatory reactions with eight antigens and 27 corresponding mAbs were used to trigger PSA, which was defined by rectal temperature. Sandwich ELISA, passive cutaneous anaphylaxis (PCA) induction and flow cytometry analysis of CD16/32 (FcγRIII/II) expression were used to characterise the ICs. The dynamic concentrations of antigen in the peripheral blood were measured by ELISA.. Only 14 of the 36 ICs could trigger PSA and thus be termed anaphylaxis-inducing immune complexes (Ai-ICs). The Ai-ICs could be characterised by constructing sandwich ELISA, inducing PCA and down-regulating CD16/32 (FcγRIII/II) expression on blood neutrophils in vitro and in vivo. Additionally, the occurrence and severity of PSA was found to be associated with the instantaneous concentration of antigen in the peripheral blood in the presence of antibody.. Only Ai-ICs, not all ICs, could trigger IgG-mediated PSA, which could be characterised by the above simple methods. The occurrence and severity of PSA was associated with the instantaneous concentration of antigen in the peripheral blood in the presence of antibody.

Topics: Anaphylaxis; Animals; Antibodies, Monoclonal; Antigen-Antibody Complex; Antigens; Disease Models, Animal; Female; Immunoglobulin G; Mice; Mice, Inbred BALB C; Ovalbumin; Random Allocation; Sensitivity and Specificity

Sensitization to food antigen can occur through cutaneous exposure.. We sought to test the hypothesis that epicutaneous sensitization with food antigen predisposes to IgE-mediated anaphylaxis on oral allergen challenge.. BALB/c mice were epicutaneously sensitized by repeated application of ovalbumin (OVA) to tape-stripped skin over 7 weeks or orally immunized with OVA and cholera toxin (CT) weekly for 8 weeks and then orally challenged with OVA. Body temperature was monitored, and serum mouse mast cell protease 1 levels were determined after challenge. Tissue mast cell (MC) counts were examined by using chloroacetate esterase staining. Levels of serum OVA-specific IgE and IgG(1) antibodies and cytokines in supernatants of OVA-stimulated splenocytes were measured by means of ELISA. Serum IL-4 levels were measured by using an in vivo cytokine capture assay.. Epicutaneously sensitized mice exhibited expansion of connective tissue MCs in the jejunum, increased serum IL-4 levels, and systemic anaphylaxis after oral challenge, as evidenced by decreased body temperature and increased serum mouse mast cell protease 1 levels. Intestinal MC expansion and anaphylaxis were IgE dependent because they did not occur in epicutaneously sensitized IgE(-/-) mice. Mice orally immunized with OVA plus CT did not have increased serum IL-4 levels, expanded intestinal MCs, or anaphylaxis after oral challenge, despite OVA-specific IgE levels and splenocyte cytokine production in response to OVA stimulation, which were comparable with those of epicutaneously sensitized mice.. Epicutaneously sensitized mice, but not mice orally immunized with antigen plus CT, have expansion of intestinal MCs and IgE-mediated anaphylaxis after single oral antigen challenge. IgE is necessary but not sufficient for food anaphylaxis, and MC expansion in the gut can play an important role in the development of anaphylaxis.

Topics: Administration, Cutaneous; Allergens; Anaphylaxis; Animals; Antibodies; Antigens; Body Temperature; Chemokine CCL2; Cholera Toxin; Food Hypersensitivity; Immunoglobulin E; Immunoglobulin G; Interleukin-4; Jejunum; Mast Cells; Mice; Mice, Inbred BALB C; Ovalbumin; Skin

Allergic inflammation and severe allergic reactions (anaphylaxis) are important in allergen induced diseases. Bacterial products such as lipopolysaccharide (LPS) are ubiquitous and can facilitate allergen induced Th2 immune responses. Phosphatase SHP-1 is critical in regulating immunological homeostasis and in allergen induced Th2 immune responses in the lung. However, the mechanisms underlying the initiation of allergic inflammation and allergen induced anaphylaxis are still not completely elucidated and it is unclear whether SHP-1 plays any role in LPS-induced airway inflammation and in allergen-induced anaphylaxis. In this study we tested the hypothesis that phosphatase SHP-1 plays an important role in allergic inflammation and anaphylaxis and determined whether its effects are through regulation of mast cell functions. SHP-1 deficient (mev/+ and mev/mev) and mast cell deficient (Kit(W-sh)) mice were examined in their responses to LPS airway stimulation and to ovalbumin (OVA) allergen induced systemic anaphylaxis. Compared to wild type mice, mev/+ mice had significantly enhanced LPS induced airway inflammation and OVA induced anaphylactic responses, including hypothermia and clinical symptoms. These changes were mast cell dependent as Kit(W-sh) mice had reduced responses whereas adoptive transfer of mast cells restored the responses. However, T and B cells were not involved and macrophages did not play a significant role in LPS induced airway inflammation. Interestingly, basophil differentiation from SHP-1 deficient bone marrow cells was significantly reduced. These findings provided evidence that through regulation of mast cell functions SHP-1 plays a critical role as a negative regulator in allergic inflammation and in allergen induced anaphylaxis. In addition, SHP-1 seems to be required for normal basophil development.

Topics: Adoptive Transfer; Allergens; Anaphylaxis; Animals; Basophils; Cell Differentiation; Cells, Cultured; Cytokines; Gene Expression; Inflammation; Injections, Intravenous; Lipopolysaccharides; Lung; Mast Cells; Mice; Mice, Knockout; Ovalbumin; Protein Tyrosine Phosphatase, Non-Receptor Type 6; Respiratory Hypersensitivity; Signal Transduction; Th2 Cells

The number of food allergy patients is increasing. Some children outgrow their food allergies through tolerance, whereas others remain susceptible throughout their lives. We aimed to contribute to food allergy therapeutics by understanding induction of oral tolerance in a murine food allergy model.. We modified an existing murine food allergy model by using ovalbumin (OVA) to induce oral tolerance, either by pretreating mice with OVA or by transferring mesenteric lymph node (MLN) cells or T cells derived from mice treated with OVA.. Pretreatment with OVA prevented food allergy, with complete suppression of OVA-specific immunoglobulin (Ig)E and IgA antibody production and interleukin (IL)-4, IL-10, and IL-9 mRNA expression. The proportion of regulatory T cells (Tregs) in MLN cells and expression of transforming growth factor-β mRNA increased. In the transfer model, anaphylaxis secondary to OVA intake was suppressed by transfer of whole MLN cells and Tregs from OVA-treated mice. However, OVA-specific IgE and IgA expressions were partially attenuated by transfer of antigen-specific and nonspecific Tregs, but not by whole MLN cells from OVA-treated mice. In the Treg transfer model, IL-4 and IL-10 mRNA expression decreased, but IL-9 mRNA expression increased.. We concluded that oral tolerance for food antigens is induced in two ways: (i) by initial exposure to antigen, or inherent tolerance, and (ii) by transfer of Tregs, or acquired tolerance. Because food allergies occur when inherent tolerance is absent, understanding of acquired tolerance is important for the development of therapies for food allergy.

Topics: Administration, Oral; Adoptive Transfer; Allergens; Anaphylaxis; Animals; Cytokines; Disease Models, Animal; Female; Food Hypersensitivity; Immune Tolerance; Immunoglobulin A; Immunoglobulin E; Mice; Mice, Inbred BALB C; Ovalbumin; T-Lymphocytes, Regulatory; Time Factors

Food-triggered anaphylaxis can encompass a variety of symptoms that affect multiple organ systems and can be life threatening. The molecular distinction between non-life-threatening and life-threatening modes of such anaphylaxis has not yet been delineated. In this study, we sought to identify the specific immune functions that regulate the severity of oral antigen-induced anaphylaxis. We thus developed an experimental mouse model in which repeated oral challenge of ovalbumin-primed mice induced an FcεRI- and IgE-dependent oral antigen-triggered anaphylaxis that involved multiple organ systems. Strikingly, the severity of the systemic symptoms of anaphylaxis (eg, hypothermia) positively correlated with the levels of intestinal mast cells (r = -0.53; P < 0.009). In addition, transgenic mice with both increased intestinal and normal systemic levels of mast cells showed increased severity of both intestinal and extra-intestinal symptoms of IgE-mediated passive as well as oral antigen- and IgE-triggered anaphylaxis. In conclusion, these observations indicate that the density of intestinal mast cells controls the severity of oral antigen-induced anaphylaxis. Thus, an awareness of intestinal mast cell levels in patients with food allergies may aid in determining their susceptibility to life-threatening anaphylaxis and may eventually aid in the treatment of food-triggered anaphylaxis.

Topics: Administration, Oral; Anaphylaxis; Animals; Antigens; Capillary Permeability; Cell Count; Diffusion Chambers, Culture; Disease Models, Animal; Food Hypersensitivity; Immunoglobulin E; Jejunum; Mast Cells; Mice; Mice, Inbred BALB C; Mice, Transgenic; Ovalbumin; Receptors, IgE; Severity of Illness Index

Nilotinib is a new orally bioavailable potent tyrosine kinase inhibitor that is used for the treatment of BCR-ABL-positive chronic myelogenous leukemia. However, its effect on mast cell-mediated anaphylactic reaction is still not known. The present study aimed to investigate the effect of nilotinib on the anaphylactic allergic reaction and study its possible mechanism(s) of action. Nilotinib administration prevented systemic anaphylaxis in mice, mediated by compound 48/80, in a dose- and time-dependent manner. Also, nilotinib significantly inhibited (P<0.05) allergic paw edema in rats. Furthermore, nilotinib significantly decreased (P<0.05) the IgE-mediated passive cutaneous anaphylaxis in a dose dependent manner. In addition, nilotinib dose-dependently reduced histamine release from the rat peritoneal mast cells activated either by compound 48/80 or by ovalbumin. Moreover, nilotinib attenuated the secretion of pro-inflammatory cytokine, tumor necrosis factor (TNF)-α expression in the rat peritoneal mast cells. These findings provide evidence that nilotinib inhibits mast cell-derived immediate-type allergic reactions and so it could be a candidate as an anti-allergic agent.

Topics: Anaphylaxis; Animals; Anti-Allergic Agents; Cytokines; Edema; Histamine Release; Hypersensitivity; Immunoglobulin E; Male; Mast Cells; Mice; Ovalbumin; p-Methoxy-N-methylphenethylamine; Protein-Tyrosine Kinases; Pyrimidines; Rats; Rats, Wistar; Tumor Necrosis Factor-alpha

To determine fluid extravasation in the splanchnic vascular bed during anaphylactic hypotension, the mesenteric lymph flow (Q(lym)) was measured in anesthetized rats sensitized with ovalbumin, along with the systemic arterial pressure (P(sa)) and portal venous pressure (P(pv)). When the antigen was injected into the sensitized rats (n = 10), P(sa) decreased from 125 ± 4 to 37 ± 2 mmHg at 10 min with a gradual recovery, whereas P(pv) increased by 16 mmHg at 2 min and returned to the baseline at 10 min. Q(lym) increased 3.3-fold from the baseline of 0.023 ± 0.002 g/min to the peak levels of 0.075 ± 0.009 g/min at 2 min and returned to the baseline within 12 min. The lymph protein concentrations increased after antigen, a finding indicating increased vascular permeability. To determine the role of the P(pv) increase in the antigen-induced increase in Q(lym), P(pv) of the nonsensitized rats (n = 10) was mechanically elevated in a manner similar to that of the sensitized rats by compressing the portal vein near the hepatic hilus. Unexpectedly, P(pv) elevation alone produced a similar increase in Q(lym), with the peak comparable to that of the sensitized rats. This finding aroused a question why the antigen-induced increase in Q(lym) was limited despite the presence of increased vascular permeability. Thus the changes in splanchnic vascular surface area were assessed by measuring the mesenteric arterial flow. The mesenteric arterial flow was decreased much more in the sensitized rats (75%; n = 5) than the nonsensitized P(pv) elevated rats (50%; n = 5). In conclusion, mesenteric lymph flow increases transiently after antigen presumably due to increased capillary pressure of the splanchnic vascular bed via downstream P(pv) elevation and perfusion and increased vascular permeability in anesthetized rats. However, this increased extravasation is subsequently limited by decreases in vascular surface area and filtration pressure.

Topics: Anaphylaxis; Animals; Antigens; Capillary Permeability; Hypotension; Lymph; Lymphatic Vessels; Male; Mesenteric Arteries; Models, Animal; Ovalbumin; Portal Pressure; Rats; Rats, Sprague-Dawley; Regional Blood Flow; Splanchnic Circulation

The clinical manifestations of food allergy include diarrhea and systemic anaphylaxis (shock), which can occur together or by themselves in different subjects. Although ingested food antigens need to be absorbed to induce shock, it is not known whether they need to be absorbed to induce diarrhea.. We sought to identify mechanisms that determine whether food allergy induces diarrhea versus shock and determine whether diarrhea requires absorption of ingested antigens.. These issues were studied in mice in active, passive, and hybrid immunization models. The active model was used to determine the allergic diarrhea susceptibility of J chain- and polymeric immunoglobulin receptor-deficient mice, which are unable to secrete IgA. The hybrid model was used to determine whether intravenously administered antigen-specific IgG antibody, which is not secreted into the gut, can protect against allergic diarrhea, as well as shock.. Shock, but not diarrhea, was induced in naive mice by using intravenous IgE anti-trinitrophenyl (TNP) antibody, followed by oral TNP-BSA, whereas both were induced in mice presensitized with intraperitoneal ovalbumin/alum plus oral ovalbumin. More TNP-BSA was required to induce shock than diarrhea in presensitized mice, and intravenous IgG anti-TNP antibody, which is not secreted into the gut, protected these mice against both diarrhea and shock. Consistent with this, chicken ovalbumin-immunized J chain- and polymeric immunoglobulin receptor-deficient mice, which have high serum IgA levels but little intestinal IgA, resisted diarrhea induction.. Intestinal immunity and oral antigen dose determine whether diarrhea, systemic anaphylaxis, or both are induced, and ingested antigen must be absorbed to induce either response.

Topics: Anaphylaxis; Animals; Clinical Protocols; Diarrhea; Disease Models, Animal; Fatty Acid-Binding Proteins; Food Hypersensitivity; Humans; Immunization; Immunoglobulin J-Chains; Immunoglobulins; Interleukin-9; Mice; Mice, Inbred BALB C; Mice, Knockout; Mice, Transgenic; Ovalbumin; Promoter Regions, Genetic; Receptors, IgG; Receptors, Polymeric Immunoglobulin; Serum Albumin, Bovine; Trinitrobenzenes

It is important to evaluate the ability of novel proteins in food crops and products to elicit potentially harmful immunologic responses, including allergic hypersensitivity. We developed a novel mouse model of food allergy involving an oral challenge of a protein antigen after feeding of the antigen in combination with modulating factors often ingested in daily life, namely, dietary oil emulsion and salicylate. In the model, BALB/c mice were sensitized orally for three weeks with ovalbumin (OVA) in linoleic acid/lecithin emulsion, followed immediately by intraperitoneal injection of sodium salicylate. At the end of the sensitization, the incidence of mice positive for serum OVA-specific IgG1 but not IgE had significantly increased in the combined-sensitization group. After the 3-week sensitization, a single or double oral challenge with OVA effectively and significantly caused severe anaphylaxis, as compared with the groups sensitized with OVA in the emulsion or the vehicle alone. Moderate increase of plasma histamine and intestinal abnormality in histology was found only in the combined-sensitization group. Anaphylaxis symptoms in the sensitized mice were induced more by oral challenge than by intravenous challenge, suggesting a critical role for the mucosal system. This is the first model for successful induction of oral anaphylaxis in mice sensitized by feeding of food protein without adjuvant. It will be useful to elucidate the mechanism of food allergy and to detect modulating factors of oral allergy at sensitization using this model, which simulates real life conditions.

Topics: Administration, Oral; Allergens; Anaphylaxis; Animals; Disease Models, Animal; Emulsions; Female; Food Hypersensitivity; Immunoglobulin G; Intestine, Small; Lecithins; Linoleic Acid; Mice; Mice, Inbred BALB C; Ovalbumin; Salicylic Acid

Clinical definition and appropriate management of anaphylaxis is a clinical challenge because there is large variability in presenting clinical signs and symptoms. Monitoring of the metabolic status of anaphylaxis may be helpful in understanding its pathophysiological processes and diagnosis. The purpose of this study was to conduct GC-MS serum metabolic profiling of anaphylaxis animal models and search for potential biomarkers of anaphylaxis. Thirty-six guinea pigs were randomly divided into an ovalbumin group (n = 12), a cattle albumin group (n = 12), and a control group (n = 12). The IgE level in the serum of the guinea pigs was evaluated by use of ELISA kits and the major metabolic changes in serum were detected by gas chromatography-mass spectrometry. Typical clinical symptoms appeared after the animals had been challenged with ovalbumin or cattle albumin. The IgE levels in serum of both model groups were significantly higher than those of the control group. Clustering trend of the three groups based on variables was observed and nine out of 858 metabolomic features were found to be significantly different between control group and model groups. Among the nine features, six features were tentatively identified as metabolites related to energy metabolism and signal transduction in anaphylaxis. In conclusion, GC-MS-based metabolic profiling analysis might be an effective auxiliary tool for investigation of anaphylaxis.

Topics: Allergens; Anaphylaxis; Animals; Biomarkers; Cattle; Energy Metabolism; Enzyme-Linked Immunosorbent Assay; Gas Chromatography-Mass Spectrometry; Guinea Pigs; Immunoglobulin E; Metabolome; Metabolomics; Models, Animal; Ovalbumin; Serum Albumin, Bovine; Signal Transduction

To explore the value of flow cytometry in anaphylactic shock diagnosis by CD63 expression being detected using flow cytometry to conform the activation of basophils.. Sixteen rats were randomly divided into two groups: control group and anaphylactic shock group. The model of anaphylactic shock rat with ovalbumin injection was established. CD63, CD45 and CD203c antibody combination, flow cytometry was employed to detected blood basophil CD63 expression. Immunofluorescence method was employed to observe the CD63 immunofluorescence staining in the rat lung tissue.. (1) Pure basophils were obtained by CD45 and CD203c gating. (2) The percentages of basophils CD63 were (17.34 +/- 2.04)% and (1.52 +/- 0.35)% in the experimental and control group, respectively. The differences between two groups were statistically significant (P < 0.01). (3) Compared with the control group, the expression of CD63 in basophils increased in anaphylactic shock lung tissue.. The detection of CD63 by flow cytometry could be the supplement of vivo allergic reactions and have good clinical value.

Topics: Anaphylaxis; Animals; Basophil Degranulation Test; Basophils; Biomarkers; Disease Models, Animal; Female; Flow Cytometry; Lung; Male; Ovalbumin; Phosphoric Diester Hydrolases; Pyrophosphatases; Random Allocation; Rats; Rats, Wistar; Tetraspanin 30

Because few curative treatments are available for food allergy, we investigated the therapeutic potential of rapamycin, a mammalian target of rapamycin (mTOR) inhibitor, on mouse food allergy.. The preventive and therapeutic effects of oral rapamycin on anaphylactic symptoms induced by oral ovalbumin (OVA) challenge in food allergy mice were investigated. Mast cell functions in response to rapamycin were also measured in the passive systemic anaphylaxis model and bone marrow-derived mast cells (BMMCs).. Daily rapamycin from the first challenge (preventive protocol) attenuated food allergy symptoms including diarrhea, anaphylactic reactions, and hypothermia in mice. The treatment decreased the challenge-induced increases in mouse mast cell protease-1 in serum and mast cell numbers in the intestine. Notably, the mice that already showed food allergy symptoms by previous challenges recovered from the disease with daily administration of rapamycin (therapeutic protocol). Anti-OVA IgG1 and IgE levels in serum, as well as IFN-γ, IL-4, IL-13, IL-9, IL-10, and IL-17 secretion from splenocytes, were decreased by the treatments. In contrast, a single dose of rapamycin failed to affect passive systemic anaphylaxis. Spontaneous and IL-9-dependent survival and IgE-induced IL-13 secretion, but not degranulation, of BMMCs were reduced by rapamycin.. Our data show that mouse food allergy was attenuated by rapamycin through an immunosuppressive effect and inhibition of intestinal mast cell hyperplasia. Inhibition of the IL-9 production-mast cell survival axis is one of the mechanisms of the therapeutic effect of rapamycin. Rapamycin and other mTOR inhibitors might be good candidates for therapeutic drugs for food allergy.

Topics: Administration, Oral; Anaphylaxis; Animals; Food Hypersensitivity; Immunosuppressive Agents; Male; Mast Cells; Mice; Mice, Inbred BALB C; Ovalbumin; Sirolimus; Treatment Outcome

The role of the hypovolemic component secondary to the microcirculatory changes in the onset of inaugural anaphylactic hypotension remains debated. We investigated the microcirculatory permeability in a model of anaphylactic shock using a fluorescence confocal microscopy imaging system.. Ovalbumin-sensitized anesthetized Brown Norway rats were randomly allocated into two groups (n = 6/group): control and anaphylaxis, respectively induced by intravenous saline or ovalbumin at time 0 (T0). The mesentery was surgically exposed. Macromolecular fluorescein isothiocyanate-dextran was intravenously injected (T0-5min) allowing in vivo visualization of the mesenteric microvascular network by fluorescence microscopy. After a period of stabilization of the contrast agent concentration, a 5-s movie was recorded to obtain baseline signal intensity. Following T0, 5-s movies were recorded every 30 s for 30 min. Capillary leakage of fluorescein isothiocyanate-dextran was assessed in interstitium and compared between groups. Data are expressed as mean ± SD.. Following anaphylactic shock onset, an early, progressive, and global signal intensity increase over time was detected in the interstitium. Mean index leakage differed between control and anaphylaxis (respectively 20 ± 11 vs. 170 ± 127%; P < 0.0001), starting at 2 min after shock onset and progressively increasing. Index leakage correlated with the drop in arterial blood pressure until T0 + 10 min (r = -0.75, P = 0.0001).. During anaphylaxis, interstitial capillary leakage occurs within minutes after shock onset. Compared with controls, the mesenteric microcirculation showed at least 8-fold-increased macromolecular capillary leakage. The inflammation-induced microcirculatory changes with subsequent intravascular fluid transfer might be involved in the onset of the inaugural hypotension during anaphylactic shock.

Topics: Anaphylaxis; Animals; Capillaries; Capillary Permeability; Hypotension; Male; Ovalbumin; Random Allocation; Rats; Rats, Inbred BN

Allergic disorders are characterized by the involvement of allergen-specific immunoglobulin (Ig)E antibodies and T helper type 2 (Th2) cells. The search for new therapies for allergic diseases has been the primary focus of interest for many investigators in recent years. Glycomacropeptide (GMP) is a biologically active component of milk that exhibits a range of immunomodulatory functions. We examined whether oral administration of GMP could affect the development of allergic sensitization and the severity of immediate cutaneous hypersensitivity reactions and of anaphylaxis. Rats treated with or without GMP were ovalbumin (OVA)-sensitized and several indicators of allergy were evaluated. Pretreatment with GMP resulted in reduction of antigen-specific IgE titre in rats when sensitized with OVA. GMP administration also markedly suppressed the proliferative response of splenocytes to antigen and the production of interleukin (IL)-13 by splenocytes of sensitized animals. In addition, GMP pretreatment attenuated the intensity of the immediate cutaneous reaction induced by antigen and protected the sensitized rats from severe anaphylaxis. These data demonstrate, for the first time, that the administration of GMP prevents allergen sensitization and reduces the severity of the early-phase reaction induced by antigen in cutaneous hypersensitivity and in anaphylaxis. GMP may be used as a novel prophylactic agent for the control of allergic diseases.

Topics: Administration, Oral; Allergens; Anaphylaxis; Animals; Antibodies; Antigens; Caseins; Dermatitis, Atopic; Humans; Immunoglobulin E; Interleukin-13; Male; Ovalbumin; Peptide Fragments; Rats; Rats, Wistar; Spleen; Th2 Cells

Anaphylactic shock in rats is characterized by antigen-induced hepatic venoconstriction and the resultant portal hypertension. We determined the role of portal hypertension in anaphylactic hypotension by using the side-to-side portacaval shunt- and sham-operated rats sensitized with ovalbumin (1 mg). We measured the mean arterial blood pressure (MAP), portal venous pressure (PVP), and central venous pressure (CVP) under pentobarbital anesthesia and spontaneous breathing. Anaphylactic hypotension was induced by an intravenous injection of ovalbumin (0.6 mg). In sham rats, the antigen caused not only an increase in PVP from 11.3 cmH(2)O to the peak of 27.9 cmH(2)O but also a decrease in MAP from 103 mmHg to the lowest value of 41 mmHg. CVP also decreased significantly after the antigen. In the portacaval shunt rats, in response to the antigen, PVP increased slightly, but significantly, to the peak of 17.5 cmH(2)O, CVP did not decrease, and MAP decreased to a lesser degree with the lowest value being 60 mmHg. These results suggest that the portacaval shunt attenuated anaphylactic portal hypertension and venous return decrease, partially preventing anaphylactic hypotension. In conclusion, portal hypertension is involved in rat anaphylactic hypotension presumably via splanchnic congestion resulting in decreased venous return and thus systemic arterial hypotension.

Topics: Anaphylaxis; Anesthesia; Animals; Antigens; Blood Pressure; Central Venous Pressure; Hypertension, Portal; Hypotension; Liver; Liver Circulation; Male; Ovalbumin; Portacaval Shunt, Surgical; Portal Pressure; Rats; Rats, Sprague-Dawley; Veins; Venous Pressure

Experimental analyses have identified strain-dependent factors that regulate susceptibility to anaphylaxis in mice. We assessed the susceptibility of the widely used 129SvEvBrd (also known as 129S5) mouse strain to IgE/mast cell-mediated anaphylaxis as compared to BALB/c. Mice were subjected to passive and oral Ovalbumin [OVA]-induced active anaphylaxis. Tissue mast cell, plasma histamine, total IgE and OVA-specific IgE levels and susceptibility to histamine i.v infusion were assessed. Bone marrow mast cell (BMMC)s were examined for FcεRI, c-kit, degranulation efficiency, proliferation, apoptosis and cytokine profile.. 129S5 mice had significantly increased susceptibility to passive and oral OVA-induced active anaphylaxis. Increased susceptibility to anaphylaxis was associated with increased homeostatic mast cell levels but not OVA-specific IgE or IgG1 levels. In vitro analyses of BMMCs revealed no difference in FcεRI and c-Kit expression, however, 129S5 BMMCs possessed greater proliferative capacity and reduced caspase-3-mediated apoptosis. IgE-BMMC degranulation assays demonstrated no difference in degranulation efficiency. Furthermore, 129S5 mice possessed increased sensitivity to histamine-induced hypothermia.. We conclude that 129S5 mice have increased susceptibility to anaphylaxis as compared to BALB/c strain and their increased susceptibility was associated with altered mast cell proliferation and homeostatic tissue levels and responsiveness to histamine. Given the wide spread usage of the 129SvEvBrd strain of mice in experimental gene targeting methodology, these data have important implications for studying IgE-reactions in mouse systems.

Topics: Anaphylaxis; Animals; Apoptosis; Body Temperature; Cell Degranulation; Cell Proliferation; Cells, Cultured; Disease Models, Animal; Female; Flow Cytometry; Histamine; Immunoglobulin E; Immunoglobulin G; Interleukin-3; Male; Mast Cells; Mice; Mice, 129 Strain; Mice, Inbred BALB C; Ovalbumin; Proto-Oncogene Proteins c-kit; Receptors, IgE

Patients treated with propranolol, a nonselective β-adrenoceptor antagonist, have increased incidence and severity of anaphylaxis. We determined whether β1- or β2-adrenoceptor antagonist modulated pulmonary vasoconstriction and bronchoconstriction in rat anaphylactic hypotension.. Anesthetized ovalbumin-sensitized male Sprague-Dawley rats were randomly allocated to the following pretreatment groups (n = 7/group): (1) sensitized control (nonpretreatment), (2) propranolol, (3) the selective β2-adrenoceptor antagonist ICI 118,551, (4) the selective β1-adrenoceptor antagonist atenolol, and (5) adrenalectomy. Shock was induced by an intravenous injection of the antigen. Mean arterial pressure, pulmonary arterial pressure, left atrial pressure, central venous pressure, portal venous pressure, airway pressure, and aortic blood flow were continuously measured.. In either sensitized control or atenolol-pretreated rats, mean arterial pressure and aortic blood flow decreased substantially, whereas pulmonary arterial pressure and airway pressure did not increase soon after antigen injection. In contrast, in rats pretreated with either propranolol, ICI 118,551, or adrenalectomy, airway pressure significantly increased by 14 cm H2O, and pulmonary arterial pressure by 7.5 mmHg after antigen injection. At 2.5 min after antigen injection, the plasma concentration of epinephrine increased 14-fold in the sensitized rats except for the adrenalectomy group. Portal venous pressure after antigen injection increased by 16 mmHg similarly in all sensitized rats. All of the sensitized control group and two of the atenolol group were alive for 60 min after antigen injection, whereas all rats of the propranolol, ICI 118,551, and adrenalectomy groups died within 50 min after antigen injection.. The pulmonary vasoconstrictive and bronchoconstrictive responses to systemic anaphylaxis were weakened via β2-adrenoceptor activation by epinephrine endogenously released from the adrenal gland in the anesthetized Sprague-Dawley rats.

Topics: Adrenalectomy; Adrenergic beta-1 Receptor Antagonists; Adrenergic beta-2 Receptor Antagonists; Anaphylaxis; Anesthesia; Animals; Aorta; Blood Pressure; Bronchoconstriction; Catecholamines; Central Venous Pressure; Coronary Circulation; Epinephrine; Heart; Hemodynamics; Male; Ovalbumin; Portal Vein; Pulmonary Artery; Rats; Rats, Sprague-Dawley; Receptors, Adrenergic, beta-2; Vascular Resistance; Vasoconstriction

The uses of drug-delivery systems in allergen specific immunotherapy appear to be a promising approach due to their ability to act as adjuvants, transport the allergens to immune-competent cells and tissues and reduce the number of administrations. The aim of this work was to evaluate the carbohydrate modified ultrafine ceramic core based nanoparticles (aquasomes) as adjuvant/delivery vehicle in specific immunotherapy using ovalbumin (OVA) as an allergen model. Prepared nanoparticles were characterized for size, shape, zeta potential, antigen integrity, surface adsorption efficiency and in vitro release. The humoral and cellular-induced immune responses generated by OVA adsorbed aquasomes were studied by two intradermal immunizations in BALB/c mice. OVA sensitized mice were treated with OVA adsorbed aquasomes and OVA adsorbed aluminum hydroxide following established protocol. Fifteen days after therapy, animals were challenged with OVA and different signs of anaphylactic shock were evaluated. Developed aquasomes possessed a negative zeta potential (-11.3 mV) and an average size of 47 nm with OVA adsorption efficiency of ~60.2 μg mg(-1) of hydroxyapatite core. In vivo immune response after two intradermal injections with OVA adsorbed aquasomes resulted in a mixed Th1/Th2-type immune response. OVA-sensitized mice model, treatment with OVA adsorbed aquasomes elicited lower levels of IgE (p<0.05), serum histamine and higher survival rate in comparison with alum adsorbed OVA. Symptoms of anaphylactic shock in OVA aquasome-treated mice were weaker than the one induced in the alum adsorbed OVA group. Results from this study demonstrate the valuable use of aquasomes in allergen immunotherapy.

Topics: Adjuvants, Immunologic; Adsorption; Allergens; Anaphylaxis; Animals; Carbohydrates; Ceramics; Desensitization, Immunologic; Drug Carriers; Drug Stability; Female; Histamine; Immunization; Mice; Mice, Inbred BALB C; Nanoparticles; Ovalbumin; Particle Size; Survival Rate

The aim of this study was to determine whether a spermine (SPM)-induced increase in gastrointestinal absorption of an allergen leads to an anaphylactic response in sensitized mice. First, we examined the enhancing effect of SPM on the gastrointestinal absorption of ovalbumin (OVA) in an in situ jejunum loop study in rats and an in vivo oral absorption study in mice. Second, we investigated whether enhancement of gastrointestinal absorption of OVA caused by SPM induces an anaphylactic response in mice sensitized to OVA. In the in situ jejunum loop study in rats, a significant amount of immune-reactive OVA was detected in the plasma after co-administration of OVA and SPM. Oral co-administration of OVA and SPM to mice in vivo also increased plasma OVA concentrations in an SPM dose-dependent manner. Furthermore, in sensitized mice, a significant increase in plasma histamine levels occurred along with the increase in plasma OVA levels after co-administration of OVA with SPM. This finding suggests that an SPM-induced increase in gastrointestinal absorption of OVA leads to an anaphylactic response. These results indicate that excess oral ingestion of SPM may have widespread health effects, including the induction of food allergies, via modulation of the function of the gastrointestinal epithelial barrier.

Topics: Anaphylaxis; Animals; Drug Synergism; Female; Histamine; Intestinal Absorption; Intestinal Mucosa; Jejunum; Male; Mice; Mice, Inbred BALB C; Ovalbumin; Rats; Rats, Sprague-Dawley; Spermine

Mast cells stimulation activates degranulation process resulting in releasing of mediators, such as histamine. In this study, the effect of aqueous extract of sitagliptin, a selective dipeptidylpeptidase-4 inhibitor, on the mast cell-mediated allergic response was studied with the possible mechanisms of action, focusing on the histamine release and pro-inflammatory cytokine secretion in mast cells. Sitagliptin produced dose dependent inhibition in compound 48/80-induced systemic reactions. In addition, sitagliptin attenuated IgE-mediated skin allergic reaction. Sitagliptin dose-dependently reduced compound 48/80- and IgE-induced histamine release from mast cells. Sitagliptin decreased the secretion of pro-inflammatory cytokines, tumor necrosis factor-α, in mast cells. So, the finding of this study provides evidence that sitagliptin inhibits mast cell derived allergic reactions, and involvement of pro-inflammatory cytokine secretion in such effects.

Topics: Anaphylaxis; Animals; Cytokines; Dose-Response Relationship, Drug; Histamine Release; Hypersensitivity; Immunoglobulin E; Male; Mast Cells; Mice; Ovalbumin; p-Methoxy-N-methylphenethylamine; Passive Cutaneous Anaphylaxis; Pyrazines; Rats; Rats, Wistar; Sitagliptin Phosphate; Triazoles; Tumor Necrosis Factor-alpha

Systemic inflammation impairs outcome in stroke patients and experimental animals via mechanisms which are poorly understood. Circulating inflammatory mediators can activate cerebrovascular endothelium or glial cells in the brain and impact on ischaemic brain injury. One of the most serious early clinical complications of cerebral ischaemia is brain oedema, which compromises survival in the first 24-48 h. It is not understood whether systemic inflammatory challenges impair outcome after stroke by increasing brain injury only or whether they have direct effects on brain oedema, cerebrovascular inflammation and blood-brain barrier damage.. We used two different systemic inflammatory stimuli, acute endotoxin treatment and anaphylaxis to study mechanisms of brain injury after middle cerebral artery occlusion (MCAo). Ischaemic brain injury, blood-brain barrier damage and oedema were analysed by histological techniques. Systemic cytokine responses and inflammatory changes in the brain were analysed by cytometric bead array, immunofluorescence, in situ hibridization and quantitative real-time PCR.. Systemic inflammatory challenges profoundly impaired survival in the first 24 h after experimental stroke in mice, independently of an increase in infarct size. Systemic lipopolysaccharide (LPS) dose-dependently increased mortality (50-100%) minutes to hours after cerebral ischaemia. Acute anaphylactic challenge in ovalbumin-sensitised mice affected stroke more seriously when induced via intraperitoneal administration compared to intravenous. Both LPS and anaphylaxis induced inflammatory changes in the blood and in the brain prior to experimental stroke. Plasma cytokine levels were significantly higher after LPS, while increased IL-10 levels were seen after anaphylaxis. After MCAo, both LPS and anaphylaxis increased microglial interleukin-1α (IL-1α) expression and blood-brain barrier breakdown. LPS caused marked granulocyte recruitment throughout the ipsilateral hemisphere. To investigate whether reduction of ischaemic damage can improve outcome in systemic inflammation, controlled hypothermia was performed. Hypothermia reduced infarct size in all treatment groups and moderately improved survival, but failed to reduce excess oedema formation after anaphylaxis and LPS-induced neuroinflammation.. Our results suggest that systemic inflammatory conditions induce cerebrovascular inflammation via diverse mechanisms. Increased brain inflammation, blood-brain barrier injury and brain oedema formation can be major contributors to impaired outcome in mice after experimental stroke with systemic inflammatory stimuli, independently of infarct size.

Topics: Anaphylaxis; Animals; Blood-Brain Barrier; Brain; Brain Edema; Brain Ischemia; Cerebral Infarction; Cytokines; Humans; Hypothermia, Induced; Infarction, Middle Cerebral Artery; Inflammation; Lipopolysaccharides; Male; Mice; Mice, Inbred C57BL; Ovalbumin; Stroke

Violacein was isolated from Chromobacterium violaceum, a soil Gram negative bacterium collected from the forest water body soil sample of Kolli Hills; Tamil Nadu, India. In the present study the immunomodulatory, analgesic and antipyretic activities of violacein were investigated in wistar rats and mice. Analgesic effect was evaluated by acetic acid- induced writhing, formalin induced paw licking and hotplate tests. Immunomodulatory effect was investigated by using ovalbumin- induced active paw anaphylaxis and sheep red blood cells (SRBC)-induced DTH tests. Antipyretic activity was evaluated by yeast- induced hyperpyrexia in rats. The anti- oedema effect was compared with indomethacin. Violacein inhibited 42.9% of ovalbumin- induced edema. Further we found that violacein (40mg/kg b.w.) reduced the edema induced by sheep red blood cells. Violacein also produced significant (p<0.05) analgesic activity in acetic acid induced writhing response, formalin induced paw licking response and hot plate analysis. Treatment with violacein showed a significant (p<0.05) dose-dependent reduction in pyrexia in rats. The results suggest that violacein possesses potent immunomodulatory, analgesic and antipyretic activities.

Topics: Acetic Acid; Analgesics; Anaphylaxis; Animals; Behavior, Animal; Chromobacterium; Dose-Response Relationship, Drug; Edema; Erythrocytes; Female; Fever; Formaldehyde; Hot Temperature; Hypersensitivity; Hypersensitivity, Delayed; Immunologic Factors; India; Indoles; Indomethacin; Male; Mice; Ovalbumin; Pain; Rats; Rats, Wistar; Sheep; Yeasts

Peptide-based immunotherapy (PIT) represents an attractive approach for targeted interventions in immunological disorders, but has not been widely explored in the context of food allergy.. In this study, we built on the information obtained from the recent identification of three immunodominant T cell epitopes of hen ovalbumin (OVA), a major egg allergen, to assess the therapeutic potential of PIT for food allergy, using the BALB/c mouse model.. Groups of mice were sensitized to OVA by repeated oral gavages, and subsequently administered with single or multiple synthetic peptides containing OVA T cell epitopes. Following the peptide administration period, all mice were orally challenged with high doses of OVA to elicit active anaphylaxis. Serum, spleen, and intestinal tissues were collected for the determination of immunoglobulin levels, cytokine secretions, and intestinal gene expression.. Significantly lower anaphylactic scores were exhibited by mice that received multiple epitope-containing peptides, accompanied by lower serum histamine and OVA-specific IgE levels, compared with placebo-treated mice. Mechanistically, the quantification of cytokine secretions in splenocyte cultures revealed a T helper type 1-biased response (IFN-gamma) in all peptide-treated mice to the detriment of a T helper type 2-response (IL-4). Interestingly, a similar cytokine expression profile was determined in intestinal tissues, accompanied by a pronounced mRNA expression of regulatory molecules TGF-beta and forkhead box transcription factor 3 (FOXP3). These data suggest the activation of local repressive mechanisms mediated by subsets of regulatory T cells.. We demonstrated the therapeutic potential of PIT in a mouse model of food allergy model and provided evidence that mechanistic pathways entailing regulatory molecules TGF-beta and FOXP3, stand as promising trails for the further understanding of peptide-based strategies for food allergy.

Topics: Amino Acid Sequence; Anaphylaxis; Animals; Cytokines; Disease Models, Animal; Egg Hypersensitivity; Epitopes, T-Lymphocyte; Forkhead Transcription Factors; Mice; Mice, Inbred BALB C; Molecular Sequence Data; Ovalbumin; Peptides; T-Lymphocytes, Regulatory; Th1 Cells; Transforming Growth Factor beta

The cytokine IL-9 has been implicated in allergic reactions, including food allergy, but its contribution to parenteral versus oral antigen-induced anaphylaxis remains unclear.. We sought to delineate the contribution of the IL-9/IL-9 receptor alpha-chain (IL-9R) pathway to parenteral and oral antigen-induced anaphylaxis.. Wild-type, IL-9-deficient (Il9(-/-)), and IL-9R-deficient (Il9R(-/-)) mice were subjected to passive and active parenteral and oral antigen (ovalbumin [OVA])-induced anaphylaxis. Severity of systemic anaphylaxis was gauged by decreased body temperature; intestinal anaphylaxis was assessed based on secretory diarrhea, intestinal mastocytosis, and serum murine mast cell protease 1 level. Specific immunoglobulin isotypes or immunoglobulin receptor-blocking antibodies were administered before challenge to define the role of the IgE and IgG pathways.. Repeated oral antigen challenge of OVA-sensitized wild-type mice induced anaphylaxis with both systemic and intestinal involvement; both were IgE dependent and attenuated in Il9(-/-) and Il9R(-/-) mice. In contrast, parenteral OVA challenge of OVA-sensitized wild-type mice induced systemic anaphylaxis, which was independent of the IL-9/IL-9R pathway. Strikingly, the IL-9/IL-9R pathway had no role in either the IgG or IgE component of parenteral antigen-induced or anti-IgE and anti-FcgammaRII/III mAb-induced systemic anaphylaxis.. Parenteral antigen-induced murine systemic anaphylaxis is mediated by both IgG- and IgE-dependent pathways, and both can occur independently of IL-9/IL-9R signaling. In contrast, oral antigen-induced intestinal and systemic anaphylaxis is strictly IgE mediated and requires IL-9/IL-9R signaling. These studies indicate differential involvement of the IL-9/IL-9R pathway in systemic and oral antigen-induced anaphylaxis.

Topics: Anaphylaxis; Animals; Enzyme-Linked Immunosorbent Assay; Immunoglobulin E; Immunoglobulin G; Infusions, Parenteral; Interleukin-9; Intestines; Mast Cells; Mice; Mice, Knockout; Ovalbumin; Receptors, Interleukin-9; Signal Transduction

Reactive oxygen species produced during allergic inflammation are key players of the pathophysiology of asthma, leading to oxidative tissue injury and inactivation of endogenous manganese superoxide dismutase (MnSOD). On this ground, removal of excess superoxide anion by scavenger molecules would be beneficial and protective. Here we show that a novel manganese(II)-containing polyamine-polycarboxylic compound, termed Mn(II)(Me(2)DO2A), with potent superoxide dismuting properties decreases the respiratory and histopathological lung abnormalities due to allergen inhalation in a model of ovalbumin (OA)-induced allergic asthma-like reaction in sensitized guinea pigs. Severe respiratory dysfunction in response to OA aerosolic challenge arose rapidly in the sensitized animals and was accompanied by bronchoconstriction, alveolar hyperinflation, mast cell activation, increased leukocyte infiltration (evaluated by myeloperoxidase assay), oxidative lung tissue injury (evaluated by the thiobarbituric-acid-reactive substances and nitrotyrosine immunostaining), decay of endogenous MnSOD activity, production of pro-inflammatory prostaglandins, and lung cell apoptosis. Treatment with Mn(II)(Me(2)DO2A) (15mg/kg, given 1h before allergen challenge), but not the inactive congener Zn(II)(Me(2)DO2A) lacking redox-active metal site, significantly attenuated all the above functional, histopathological and biochemical parameters of allergic inflammation and restored the levels of MnSOD activity. In conclusion, our findings support the potential therapeutic use of Mn(II)(Me(2)DO2A) as novel superoxide scavenger drug in asthma and anaphylactic reactions.

Topics: Allergens; Anaphylaxis; Animals; Anti-Asthmatic Agents; Apoptosis; Asthma; Bronchoconstriction; Caspase 3; Free Radical Scavengers; Guinea Pigs; Male; Mast Cells; Organometallic Compounds; Ovalbumin; Peroxidase; Superoxides; Thiobarbituric Acid Reactive Substances; Tyrosine

1. Exercise training attenuates circulatory shock due to haemorrhage, endotoxin or heatstroke. However, it remains unknown whether exercise training attenuates anaphylactic shock. Hepatic venoconstriction is involved in rat anaphylactic hypotension. In the present study, we determined the effects of exercise training on both anaphylaxis-induced segmental venoconstriction in rat perfused livers and systemic anaphylaxis in conscious rats. The role of nitric oxide (NO) in the effect of exercise on the venoconstriction of perfused livers was also examined. 2. Rats were subjected to running training on a motorized treadmill for 4 weeks. Two weeks prior to the anaphylaxis experiment, Sprague-Dawley rats were actively sensitized with the antigen ovalbumin. In isolated livers perfused portally with blood, the portal venous pressure (P(pv)) and sinusoidal pressure were measured to determine the pre- and post-sinusoidal resistances (R(pre) and R(post), respectively). In conscious rats, systemic arterial pressure (SAP) and P(pv) were determined. 3. In the perfused livers of sedentary rats, antigen administration led to a predominant presinusoidal constriction, as evidenced by 4.6- and 1.7-fold increases in R(pre) and R(post), respectively. The anaphylaxis-induced increase in R(pre) was significantly attenuated by 24% by exercise training. Inhibition of NO synthase with N(G)-nitro-L-arginine methyl ester (100 micromol/L) 10 min prior to the injection of antigen enhanced anaphylactic venoconstriction, but did not alter the effect of exercise training on the increase in R(pre). In contrast, exercise training did not attenuate either anaphylactic hypotension or portal hypertension in conscious rats. 4. In conclusion, exercise training attenuates the anaphylaxis-induced presinusoidal constriction in rat isolated perfused livers, independent of NO production. However, this action is not evident in conscious rats and exercise training does not affect anaphylactic hypotension in conscious rats.

Topics: Anaphylaxis; Animals; Enzyme Inhibitors; Hypotension; Liver; Liver Circulation; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide; Ovalbumin; Perfusion; Physical Conditioning, Animal; Portal Pressure; Rats; Rats, Sprague-Dawley; Vascular Resistance; Vasoconstriction

The purpose of this study was to evaluate the effects of feeding a low dose of lipoic acid on attenuating soybean beta-conglycinin-induced hypersensitivity using a rat model, with ovalbumin as the positive allergic control. Forty-eight recently weaned male Sprague-Dawley rats were assigned to four treatments and fed a cornstarch-casein-based diet either unsupplemented (Groups I, II and III) or supplemented with 25 mg/kg lipoic acid (Group IV). On days 1, 10, 17, and 24, Groups III and IV were sensitised with 20 mg beta-conglycinin by means of intragastric gavage, while Group II was sensitised with 20 mg ovalbumin and Group I (control) with casein. On day 31, rats received a double dose of beta-conglycinin, ovalbumin or casein, respectively. Ovalbumin-sensitised rats (Group II) and beta-conglycinin-sensitised rats (Group III) demonstrated an increase in serum IgE and histamine release, but reduced growth performance compared to the control (Group 1) (p < 0.05). A low dose of lipoic acid had no effect on average weight gain, but increased villus height in the jejunum (p < 0.05), while reducing serum beta-conglycinin-specific IgE and histamine content in the jejunum. Moreover, lipoic acid supplementation did not significantly affect interferon-gamma or interleukin-4. Taken together, our results suggest that a low dose of lipoic acid could potentially be used as an immunomodulator to attenuate soybean beta-conglycinin induced allergies.

Topics: Anaphylaxis; Animal Feed; Animals; Antigens, Plant; Dose-Response Relationship, Drug; Globulins; Histamine; Immunoglobulin E; Intestine, Small; Male; Ovalbumin; Rats; Rats, Sprague-Dawley; Seed Storage Proteins; Soybean Proteins; Spleen; Thioctic Acid

Thymic stromal lymphopoietin (TSLP) is a cytokine produced by epithelial cells that acts on dendritic cells, mast cells, T cells, and B cells. TSLP is involved in the pathogenesis of allergic inflammation in the lung and skin, but data indicate a regulatory role in the gastrointestinal tract. We tested the functional role of TSLP in mouse models of gastrointestinal allergy and tolerance.. TSLP Receptor (TSLPR)(+/+) and TSLPR(-/-) mice were sensitized and challenged with ovalbumin; models of allergic diarrhea or systemic anaphylaxis were studied. To induce oral tolerance, mice were fed with low-dose ovalbumin before they were immunized with it. Tolerance was measured from inhibition of ear swelling in a delayed-type hypersensitivity reaction.. TSLPR(-/-) mice were protected from the onset of allergic diarrhea; they did not develop mastocytosis in the jejunum and had reduced ovalbumin-immunoglobulin E in their serum, compared with TSLPR(+/+) mice. TSLPR(-/-) mice also lost T helper cell (Th) 2-mediated inflammation in the jejunum. In contrast, sensitization and oral tolerance were not impaired in TSLPR(-/-) mice. Transfer of wild-type, Th2-primed cells to TSLPR(-/-) mice completely restored the development of allergic diarrhea. Antigen presentation assays showed that TSLPR on T cells, but not dendritic cells, was required to mediate the Th2 response.. TSLP is required for allergic inflammation but not primary sensitization or tolerance to food proteins in the gastrointestinal tract; it amplifies Th2 responses directly from CD4(+) T cells.

Topics: Anaphylaxis; Animals; Cytokines; Dendritic Cells; Diarrhea; Food Hypersensitivity; Gastrointestinal Tract; Immune Tolerance; Mice; Mice, Inbred BALB C; Ovalbumin; Th2 Cells; Thymic Stromal Lymphopoietin

The prevalence of allergic disorders is increasing in industrial areas and countries. Recent reports suggest that some environmental pollutants are related to the increase in allergic diseases, and we reported that trichloroethylene (TCE) is a candidate chemical for causing the increase of allergic diseases, as TCE ingestion is associated with allergic reaction enhancement. TCE is widely used in many industries, and it is commonly detected as an environmental contaminant. This study aimed to clarify the immunotoxicity of TCE in detail. BALB/c mice were treated with TCE dissolved in drinking water for 2 and 4 weeks, and the mice were immunized with ovalbumin (OVA)/aluminum hydroxide (alum) twice. On the final day of the TCE exposure period, we measured the active cutaneous anaphylaxis (ACA) reaction and the antigen- specific IgE level in serum as well as the histamine level at the allergic reaction site and assayed the proliferation rates of splenocytes collected from the animals. The ACA reaction was enhanced by TCE ingestion. The OVA specific IgE level in mice was enhanced by TCE exposure for 4 weeks. The proliferation rate of the splenocytes was enhanced by TCE ingestion for 2 and 4 weeks. The enhancement of the ACA reaction by TCE ingestion via drinking water may be related to the increase in splenocyte proliferation. On the other hand, it may be weakly related to antigen-specific IgE production.

Topics: Anaphylaxis; Animals; Body Weight; Cell Proliferation; Cytokines; Disease Models, Animal; Drinking; Histamine; Hypersensitivity, Immediate; Immunity, Active; Immunoglobulin E; Male; Mice; Mice, Inbred BALB C; Ovalbumin; Spleen; Trichloroethylene; Water Pollutants, Chemical

Systemic anaphylaxis is an acute, severe, and potentially fatal allergic reaction. Two classes of antibodies, IgE and IgG, contribute to the development of anaphylaxis in mice, through different mechanisms with distinct usage of effector cells and chemical mediators. Larger quantities of antibody and antigen are reportedly required to induce IgG-mediated anaphylaxis than IgE-mediated one, suggesting that the former may not happen as frequently as the latter in real life. To readdress this issue, we established in the present study a novel mouse model of passive IgG-mediated systemic anaphylaxis to a native protein antigen, ovalbumin (OVA), rather than artificially haptenated protein antigens used in previous studies. Passive sensitization of mice with a cocktail of but not individual IgG1 mAbs specific to distinct OVA epitopes elicited systemic anaphylaxis in response to OVA challenge. Importantly, much smaller doses of antibody and antigen than previously reported were sufficient for the induction of IgG-mediated systemic anaphylaxis. Moreover, a relatively small dose of antigen could induce severe anaphylaxis through both IgE- and IgG-mediated mechanisms when mice had been passively sensitized with antigen-specific IgE and IgG. These results strongly suggest that IgG-mediated systemic anaphylaxis is not rare among antibody-mediated systemic anaphylaxis, in contrast to previous thought, and significantly contributes to active systemic anaphylaxis in real life, at least in mice.

Topics: Anaphylaxis; Animals; Antibodies; Antibodies, Monoclonal; Antigens; Disease Models, Animal; Female; Immunoglobulin E; Immunoglobulin G; Mice; Mice, Inbred C57BL; Ovalbumin

Topics: Adolescent; Adult; Age Factors; Anaphylaxis; Child; Child, Preschool; Drug Compounding; Egg Hypersensitivity; Female; Humans; Infant; Influenza A virus; Influenza Vaccines; Influenza, Human; Male; Middle Aged; Ovalbumin; Practice Guidelines as Topic

The number of patients with food allergy has increased dramatically over the last several decades. However, there is no effective drug for food allergies. In the present study, we evaluated the effects of kakkonto, a traditional Japanese herbal medicine, in a mouse model of food allergy with gastrointestinal symptoms.. BALB/c mice were systemically sensitized twice with ovalbumin (OVA) and then were repeatedly given OVA by oral intubation (OVA mice). Kakkonto was administered orally before the OVA challenges.. The OVA mice developed allergic diarrhea (91.8 +/- 3.8% after 6 OVA challenges), and myeloperoxidase (MPO) activity was dramatically elevated in the colons of the OVA mice. Kakkonto significantly suppressed the occurrence of allergic diarrhea and MPO activity in the OVA mice. Furthermore, the number of mucosal mast cells was greatly increased in the proximal colons of the OVA mice, and this was also suppressed by kakkonto. Interestingly, mRNA expression of helper T cell type 1 (Th1) cytokines (IFN-gamma) and Th2 cytokines (IL-4, IL-5 and IL-10) were significantly upregulated in the proximal colons of the OVA mice, an effect which was also reduced by kakkonto. Transcriptome analysis detected increased mRNA expression of suppressor of cytokine signaling-3 in the proximal colons of OVA mice, which was decreased by kakkonto administration.. Kakkonto has immunosuppressive effects and interferes with the infiltration of mucosal mast cells in the colons of mice with induced food allergy, leading to improvement of allergic symptoms. Kakkonto has potential as a therapeutic drug for treatment of allergic symptoms induced by the disruption of intestinal mucosal immunity.

Topics: Anaphylaxis; Animals; Cell Movement; Chemokines; Chymases; Colon; Diarrhea; Disease Models, Animal; Drugs, Chinese Herbal; Food Hypersensitivity; Gene Expression; Gene Expression Profiling; Immunoglobulin E; Interleukins; Intestinal Mucosa; Male; Mast Cells; Mice; Mice, Inbred BALB C; Ovalbumin; Peroxidase; Phytotherapy; Suppressor of Cytokine Signaling 3 Protein; Suppressor of Cytokine Signaling Proteins

Food allergy can cause food-related anaphylaxis. Food allergen labeling is the principal means of protecting sensitized individuals. This motivated European Directive 2003/89 on the labeling of ingredients or additives that could trigger adverse reactions, which has been in effect since 2005. During this study, we developed animal models with allergy to ovalbumin, caseinate, and isinglass in order to be able to detect fining agent residues that could induce anaphylactic reactions in sensitized mice. The second aim of the study was to design sandwich ELISA tests specific to each fining agent in order to detect their residue antigenicity, both during wine processing and in commercially available bottled wines. Sensitized mice and sandwich ELISA methods were established to test a vast panel of wines. The results showed that although they were positive to our highly sensitive sandwich-ELISA tests, some commercially available wines are not allergenic in sensitized mice. Commercially available bottled wines made using standardized processes, fining, maturation, and filtration, do not therefore represent any risk of anaphylactic reactions in sensitized mice.

Topics: Allergens; Anaphylaxis; Animals; Caseins; Cattle; Chickens; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Female; Fishes; Food Hypersensitivity; Gelatin; Humans; Mice; Mice, Inbred Strains; Ovalbumin; Rabbits; Wine

Two major drawbacks of current subcutaneous specific immunotherapy are the risk to induce severe anaphylactic reactions and the need of multiple injections of the allergen to reduce IgE-mediated hypersensitivity. The sustained release of allergens over time provided by poly(lactide-co-glycolide) microparticles (MP) could mimic the current therapeutic schedule and decrease their allergenicity. Moreover, MP could also co-deliver Th1 immunoadjuvants, such as CpG motifs.. Ovalbumin (OVA)-sensitized BALB/c mice were treated intradermally with OVA or OVA plus CpG containing MP. OVA-specific IgG1 and IgG2a as well as IgE total levels and cytokine production were assessed throughout the experiment. The protection exerted by the MP against allergen challenge was estimated with body temperature changes, mortality and other symptoms.. Microparticulated treatments, irrespective of the presence of CpG motifs, elicited a lower IgE/IgG2a ratio than those induced by the allergen in solution (free or with adjuvants). However, after induction of the anaphylactic shock, only mice treated with MP co-encapsulating OVA plus CpG showed a significant lower decrease in body temperature and were totally protected from death. Mice that were injected with OVA plus CpG in solution or with Alum displayed a marked fall of temperature accompanied by high mortality rates (70-100%).. MP encapsulating both OVA, as an allergen model, and CpG sequences, as a pro-Th1 adjuvant, decreased the risk for OVA sensitization (IgE induction) and protected sensitized mice from anaphylactic shock after allergen provocation. Therefore, the combination of allergens and CpG sequences into MP could perform a safer alternative to current specific immunotherapy.

Topics: Adjuvants, Immunologic; Allergens; Anaphylaxis; Animals; Desensitization, Immunologic; Disease Models, Animal; Drug Carriers; Immunoglobulin E; Immunoglobulin G; Interferon-gamma; Interleukin-4; Lymph Nodes; Mice; Mice, Inbred BALB C; Oligodeoxyribonucleotides; Ovalbumin; Polyglactin 910; Spleen

Exposure to antigens of the fish parasite Anisakis is associated with the development of protein contact dermatitis in seafood-processing workers. Understanding the basic mechanisms controlling allergic sensitization through the skin is critical for designing therapies that will prevent the progression of allergic disease.. To investigate the roles of interleukin (IL)-4, IL-13 and the IL-4Ralpha in both local skin pathology and systemic sensitization following epicutaneous exposure to Anisakis proteins.. BALB/c wild-type (WT) mice and mice deficient in IL-4, IL-13 or IL-4 and IL-13, as well as mice with cell-specific impairment of IL-4Ralpha expression, were sensitized to Anisakis antigen by repeated epicutaneous application of Anisakis extract. Following this sensitization, skin pathology was recorded and systemic responses were investigated. Intravenous challenge with Anisakis extract was performed to test for the development of biologically relevant systemic sensitization.. In WT mice, epicutaneous sensitization with Anisakis larval antigens induced localized inflammation, epidermal hyperplasia, production of T(H)2 cytokines, antigen-specific IgE and IgG1. Intravenous challenge of sensitized mice resulted in anaphylactic shock. Interestingly, IL-13 deficient mice failed to develop epidermal hyperplasia and inflammation, whilst anaphylaxis was reduced only in strains deficient either in IL-4 only, or deficient in IL-4 and IL-13 concurrently, as well as in mice deficient in IL-4Ralpha or with impaired IL-4Ralpha expression on CD4(+) T cells.. Interleukin-13 plays a central role in protein contact dermatitis associated with repeated epicutaneous exposure to Anisakis extract, whereas IL-4 drives systemic sensitization and resultant anaphylactic shock.

Topics: Allergens; Anaphylaxis; Animals; Anisakis; Antibodies, Protozoan; Antigens, Helminth; CD4-Positive T-Lymphocytes; Dermatitis, Contact; Immunoglobulin E; Immunoglobulin G; Interleukin-13; Interleukin-4; Interleukin-4 Receptor alpha Subunit; Mice; Mice, Inbred BALB C; Mice, Knockout; Ovalbumin; Skin

Allium cepa (Family Liliaceae) is a reputed Indian medicinal herb that is prescribed as an effective remedy for several ailments in the Ayurvedic system of medicine. The aim of this study was to evaluate its efficacy against various events responsible for Type I allergic reactions. A herbal fraction (ALC-02) from A. cepa (bulb) inhibited histamine release and attenuated intracellular calcium levels in Compound 48/80-induced rat peritoneal mast cells. It also prevented Compound 48/80-mediated systemic anaphylaxis while lowering histamine levels in plasma. ALC-02 suppressed carrageenan-induced rat paw edema. It inhibited eosinophil peroxidase activity and protein content in bronchoalveolar lavage fluid (BALF) of ovalbumin-challenged mice. In this experiment ALC-02 also caused a substantial reduction in lipid peroxidation in BALF/lung tissue and augmented superoxide dismutase activity in lung tissue. ALC-02 suppressed erythrocytic lysis caused by Triton X-100. A significant quenching of 1,1-diphenyl-2-picrylhydrazyl radical by ALC-02 was observed. The results have shown a promising anti-allergic profile of ALC-02 that could be attributed to its potential antihistaminic, anti-inflammatory, and antioxidant activities.

Topics: Anaphylaxis; Animals; Anti-Allergic Agents; Anti-Inflammatory Agents; Antioxidants; Biphenyl Compounds; Bronchoalveolar Lavage Fluid; Calcium; Edema; Eosinophil Peroxidase; Erythrocytes; Histamine; Histamine Antagonists; Lipid Peroxidation; Mast Cells; Mice; Mice, Inbred BALB C; Onions; Ovalbumin; Picrates; Plant Extracts; Plant Roots; Rats; Rats, Wistar; Superoxide Dismutase

There are presented the results of genotoxicologic, immunologic and allergologic examinations which were conducted within the framework of integrated medical and biological assessment of genetically modified rootworm Diabrotica spp.-protected maize event MIR604. Analysis of damages of DNA and structural chromosome aberrations, assessment of the allergenic potential and immunoreactive properties has not confirmed any genotoxic, allergenic and immunotoxic effect of maize event MIR604.

Topics: Anaphylaxis; Animals; Bone Marrow Cells; Chromosome Aberrations; Colon; Comet Assay; DNA Damage; Food Analysis; Food Hypersensitivity; Food, Genetically Modified; Hypersensitivity, Delayed; Liver; Male; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; Ovalbumin; Plants, Genetically Modified; Rats; Rats, Wistar; Species Specificity; Toxicity Tests; Zea mays

Hepatic venoconstriction plays a significant role in anaphylactic hypotension in anesthetized rats. The purpose of this study is to determine whether the primary site of anaphylactic venoconstriction in the liver venous circulation occurs prior to or distal to the sinusoidal capillaries. We also determined whether the hepatic blood volume is increased during anaphylactic hypotension.. We measured, using a servo-null micropipette pressure-measuring system, the hepatic venular transmural pressure (P micro hv) at the liver surface of anesthetized rats sensitized with the antigen of ovalbumin (1 mg). We also measured the liver lobe thickness, using the ultrasonic crystal dimension measuring system. Anaphylactic hypotension was induced by an intravenous injection of 0.6 mg ovalbumin.. When the antigen was injected, the systemic arterial pressure decreased profoundly from 118+/-9 to 45+/-4 mm Hg, which was accompanied by an increase in Ppv and P micro hv: P micro hv only transiently increased from 3.1+/-0.9 to 8.8+/-1.5 cm H(2)O at 1 min and then rapidly returned to the baseline within 2 min, when Ppv continued to increase and reached the peak of 36+/-7 cm H(2)O at 3.5 min after antigen. This greater increase in Ppv-to-P micro hv gradient than that in P micro hv-to-Pcv gradient after antigen indicated that the constriction of the portal veins and the sinusoids much predominates over that of the hepatic veins. Along with this hepatic pre- and sinusoidal constriction, the liver lobe thickness significantly decreased by 4% after antigen.. Pre-sinusoidal constriction during anaphylactic shock in anaesthetized rats increased the portal venous pressure while the hepatic venular pressure only increased slightly and transiently. This predominant pre-sinusoidal constriction is accompanied by a decrease in liver volume.

Topics: Anaphylaxis; Anesthesia; Animals; Antigens; Blood Pressure; Blood Volume; Hepatic Veins; Hypotension; Liver; Liver Circulation; Male; Organ Size; Ovalbumin; Portal Pressure; Portal Vein; Rats; Rats, Sprague-Dawley; Time Factors; Vasoconstriction; Veins; Venous Pressure

The adjuvant and protective capacity against anaphylactic shock of the association between rough lipopolysaccharide of Brucella ovis (LPS) coencapsulated with ovalbumin (OVA), as a model allergen, in Gantrez AN nanoparticles was investigated. Several strategies were performed in order to study the adjuvant effect of the LPS either encapsulated or coating the nanoparticles. OVA, as well as LPS, was incorporated either during the manufacturing process (OVA-encapsulated or LPS-encapsulated nanoparticles, respectively) or after the preparation (OVA-coated or LPS-coated nanoparticles, respectively). After the administration of 10 microg of OVA incorporated in the different formulations, all the nanoparticles, with or without LPS, were capable of amplifying the immune response (IgG(1) and IgG(2a)). However, in a model of sensitized mice to OVA, the formulation with OVA and LPS-entrapped inside the nanoparticles administered intradermally in three doses of 3 microg of OVA each was the only treatment that totally protected the mice from death after a challenge with an intraperitoneal injection of OVA. In contrast, the control group administered with OVA adsorbed onto a commercial alhydrogel adjuvant showed 80% mortality. These results are highly suggestive for the valuable use of Gantrez nanoparticles combined with rough LPS of B. ovis in immunotherapy.

Topics: Adjuvants, Immunologic; Allergens; Anaphylaxis; Animals; Brucella ovis; Drug Carriers; Drug Compounding; Female; Immunization Schedule; Immunoglobulin G; Injections, Intradermal; Interleukin-10; Lipopolysaccharides; Maleates; Mice; Mice, Inbred BALB C; Nanoparticles; Ovalbumin; Polyvinyls; Time Factors

We determined the roles of platelet-activating factor (PAF) and histamine in anaphylactic hypotension in ovalbumin-sensitized anesthetized BALB/c mice. The effects of PAF and histamine on hemodynamic variables were studied by measuring the systemic arterial (Psa), portal venous (Ppv) and central venous (Pcv) pressures. Intravenous PAF evoked a biphasic Psa response, an initial rapid and transient drop followed by marked hypotension, accompanied by a decrease in Pcv. Histamine caused only mild systemic hypotension. Both agents similarly increased Ppv by approximately 4 cm H(2)O at high doses. After an injection of antigen, Psa initially increased slightly and then decreased from the baseline of 94 +/- 1 mm Hg to 46 +/- 1 mm Hg at 10 min after antigen administration, with Pcv decreasing by 2.5 cm H(2)O. Ppv increased by 3.5 cm H(2)O at 5 min after antigen injection. Pretreatment with either CV-6209 (PAF receptor antagonist, 1 mg/kg) or diphenhydramine (histamine H(1) receptor antagonist, 20 mg/kg) significantly attenuated an antigen-induced decrease in Psa. The inhibitory action of CV-6209 was greater than that of diphenhydramine, and the combination of these 2 antagonists almost completely inhibited the anaphylactic hypotension. In contrast, the antigen-induced increase in Ppv was attenuated by CV-6209 alone but augmented by diphenhydramine. It is concluded that anaphylactic hypotension is mainly mediated by PAF and, to a lesser extent, by histamine in anesthetized BALB/c mice.

Topics: Anaphylaxis; Animals; Blood Pressure; Diphenhydramine; Histamine; Histamine H1 Antagonists; Hypotension; Male; Mice; Mice, Inbred BALB C; Ovalbumin; Platelet Activating Factor; Platelet Membrane Glycoproteins; Pyridinium Compounds; Receptors, G-Protein-Coupled; Receptors, Histamine H1

The bee pollen is used in folk medicine to alleviate allergic reactions. The bee pollen phenolic extract (BPPE) consists in phenolic compounds (flavonoids) from plants picked by Apis mellifera bee.. Here we evaluated the anti-allergic property of the BPPE and the flavonoid myricetin (MYR) in murine model of ovalbumin (OVA)-induced allergy.. The study focused on the BPPE or myricetin treatment of OVA-sensitized BALB/c mice and their effects on the IgE and IgG1 production, pulmonary cell migration, eosinophil peroxidase (EPO) activity and anaphylactic shock reaction.. The BPPE treatment (200mg/kg) showed inhibition of the paw edema, IgE and IgG(1) OVA-specific production, leukocyte migration to the bronchoalveolar lavage (BAL) and EPO activity in lungs. In addition, BPPE treatment showed partial protection on the anaphylactic shock reaction induced by OVA. Treatment with myricetin (5 mg/kg) also inhibited pulmonary cell migration and IgE and IgG(1) OVA-specific production.. These results support the hypothesis the myricetin is one of the flavonoids of BPPE responsible for the anti-allergic effect and a potential tool to treat allergies.

Topics: Anaphylaxis; Animals; Anti-Allergic Agents; Bees; Bronchoalveolar Lavage Fluid; Cell Movement; Disease Models, Animal; Eosinophil Peroxidase; Female; Flavonoids; Immunoglobulin E; Immunoglobulin G; Leukocytes; Male; Mice; Mice, Inbred BALB C; Ovalbumin; Plant Extracts; Pollen; Rats; Rats, Wistar

Previously, we reported the immunosuppressive action of the aqueous extract of Kalanchoe pinnata (Kp) in mice. In the present study, we report on the protective effect of Kp in fatal anaphylactic shock, likewise a Th2-driven immunopathology, and the identification of its active component. Mice daily treated with oral Kp during hypersensitization with ovalbumin were all protected against death when challenged with the allergen, as compared with the 100% mortality in the untreated group. A single intraperitoneal dose 3 h prior to challenge was partially effective. Oral protection was accompanied by a reduced production of OVA-specific IgE antibodies, reduced eosinophilia, and impaired production of the IL-5, IL-10 and TNF-alpha cytokines. In vitro, Kp prevented antigen-induced mast cell degranulation and histamine release. Oral treatment with the quercitrin flavonoid isolated from Kp prevented fatal anaphylaxis in 75% of the animals. These findings indicate that oral treatment with Kp effectively downmodulates pro-anaphylactic inducing immune responses. Protection achieved with quercitrin, although not maximal, suggests that this flavonoid is a critical component of Kp extract against this extreme allergic reaction.

Topics: Anaphylaxis; Animals; Cytokines; Eosinophilia; Immunoglobulin E; Immunosuppressive Agents; Kalanchoe; Lymphocyte Activation; Male; Mast Cells; Mice; Mice, Inbred BALB C; Ovalbumin; Phytotherapy; Plant Extracts; Quercetin; Rats; Th2 Cells

Asthma is a chronic inflammatory disorder of the airways. The available treatment options have major limitations owing to low efficacy, associated adverse events and compliance issues. Therefore, the health burden of bronchial asthma is increasing globally at an alarming rate, providing a strong impetus for the development of new therapeutics. Myrica sapida is known traditionally in Ayurveda to possess anti-asthmatic activity. Hence, the present investigation was undertaken to evaluate the bronchodilator and anti-anaphylactic activity of the stem bark of Myrica sapida.. Experimental models studied were acetylcholine induced bronchospasm in guinea pigs, egg albumin induced anaphylaxis in guinea pigs, in vitro studies on tracheal strip of egg albumin sensitized guinea pigs.. Treatment with ethanolic extract of M. sapida, 75 mg/kg, orally resulted in significant protection against acetylcholine aerosol induced bronchospasm and allergen induced anaphylaxis in guinea pigs. Ethanolic extract of M. sapida (75 mg/kg, p.o.) prevented the potentiation of responses and also produced a decrease in pD2 value of histamine and acetylcholine in guinea pig tracheal strip.. These results suggest that M. sapida possesses bronchodilator activity, has potent inhibitory effect on immediate hyper-sensitivity reactions and decreases bronchial hyper-responsiveness.

Topics: Acetylcholine; Aerosols; Anaphylaxis; Animals; Bronchial Spasm; Bronchodilator Agents; Guinea Pigs; In Vitro Techniques; Muscle Contraction; Muscle, Smooth; Myrica; Ovalbumin; Phytotherapy; Plant Extracts; Rats

Caffeic acid phenethyl ester (CAPE) is an active component of honeybee propolis extracts. It has several positive effects, including anti-inflammatory, anti-oxidation, anti-cancer, anti-bacterial, anti-viral, anti-fungal, and immunomodulatory effects. In particular, the suppressive effect of NF-kappaB may disrupt a component of allergic induction. The principal objective of this experimental study was to evaluate the effects of CAPE on the active systemic anaphylaxis induced by ovalbumin (OVA) challenge in mice. Mice were intraperitoneally sensitized and intravenously challenged with OVA. Histopathological analysis, nuclear factor (NF)-kappaB activation, and the plasma levels of histamine and total IgE after allergen challenge were evaluated. After challenges, all of the sham-treated mice developed anaphylactic symptoms, increased plasma levels of histamine and OVA-specific IgE, marked vascular leakage, NF-kappaB activation, platelet-activating factor (PAF) production, and histological changes including pulmonary edema and hemorrhage in the renal medullae within 20 min. By way of contrast, a reduction in the plasma levels of histamine and OVA-specific IgE and an inhibition of NF-kappaB activation and PAF release were observed in the CAPE-treated mice. In addition, a significant prevention of hemoconcentration and OVA-induced pathological changes were noted. These results indicate that CAPE demonstrates an anti-allergic effect, which may be the result of its protective effects against IgE-mediated allergy.

Topics: Anaphylaxis; Animals; Anti-Allergic Agents; Caffeic Acids; Disease Models, Animal; Female; Histamine Release; Immunoglobulin E; Mice; Mice, Inbred ICR; NF-kappa B; Ovalbumin; Phenylethyl Alcohol; Tumor Necrosis Factor-alpha

Many types of fermented food are consumed in Japan. Although some are produced by plant-origin lactic-acid bacteria (LAB) fermentation, the physiological functions of such bacteria remain unclear. We therefore isolated LAB of plant origin from Kyoto pickles and determined the immunological activity of heat-killed preparations of plant-origin LAB.. The Lactobacillus pentosus strain S-PT84 was selected from among 16 LAB of plant origin as the strongest interleukin (IL)-12-inducing strain. IL-12- and IL-10-inducing activities were determined with macrophages from BALB/c mice. The in vivo immunomodulating effect of S-PT84was determined with BALB/c mice fed S-PT84. The antiallergic activity of S-PT84 was examined in ovalbumin (OVA)/alum-administered BALB/c mice.. The L. pentosus strain S-PT84 induced production of both IL-12 and IL-10 in vitro. S-PT84 enhanced splenic natural-killer activity and modulated the T helper (Th) type 1/type 2 balance toward a Th1-dominant state. In the OVA-induced allergy model, orally administered S-PT84 lowered serum IgE levels and suppressed active cutaneous anaphylaxis reaction and splenic IL-4 production. IL-10 production from splenocytes of OVA-immunized mice was upregulated by feeding S-PT84.. Despite heat-killing, S-PT84 exhibited antiallergic effects by modulating the Th1/Th2 balance and inducing regulatory T cells. The L. pentosus strain S-PT84, which is of plant origin and isolated from a traditional Japanese food, is expected to be useful for treatment of many immune diseases including allergies, tumors, infectious diseases and auto-immune diseases.

Topics: Allergens; Anaphylaxis; Animals; Anti-Allergic Agents; Cells, Cultured; Dermatitis, Atopic; Disease Models, Animal; Food Hypersensitivity; Food Microbiology; Hot Temperature; Immunoglobulin E; Immunosuppressive Agents; Interleukin-10; Interleukin-12; Killer Cells, Natural; Lactobacillus; Male; Mice; Mice, Inbred BALB C; Ovalbumin; Probiotics; Spleen; T-Lymphocytes, Regulatory; Th1 Cells; Th2 Cells; Up-Regulation

Allergic inflammation is induced by type 2 T helper cell (Th2) and Th2 cytokines such as interleukin (IL)-4, IL-5 and IL-13. These cytokines induce the production of allergen-specific immunoglobulin (Ig)E by B cells, and the ensuing degranulation of mast cells via IgE cross-linking leads to most clinical manifestations of allergic diseases. We examined the ability of immunomodulatory unmethylated CpG oligodeoxynucleotides (ODN), which are potent inducers of Th1 cytokines, to prevent allergic symptoms in mice immunized and sensitized with allergen. Coadministration of CpG ODN with ovalbumin (OVA) before OVA sensitization substantially prevented mice from allergic anaphylaxis representing enhanced circulating concentrations of OVA-specific IgE and histamine, and decreased body temperature. Although CpG ODN provokes an abundance of Th1-skewing cytokines, including IL-12, interferon (IFN)-alpha and IFN-gamma, administration of CpG ODN in IFN-gamma deficient mice inhibited IgE production and prevented from OVA-induced anaphylaxis, indicating a dispensable role of IFN-gamma in mediating these protective effects. In vitro analysis revealed that CpG ODN inhibited class switching from IgM to IgE and IgG1 in response to CD40 and IL-4 in B cells, and this effect did not correlate with up-regulation of IFN-alpha production. These results imply a B cell-intrinsic, T cell-independent mechanism by which CpG ODN directly acts on B cells and inhibits IgE and IgG1 production leading to cause prevention from allergic symptoms.

Topics: Adjuvants, Immunologic; Anaphylaxis; Animals; B-Lymphocytes; Immunoglobulin Class Switching; Mice; Mice, Inbred C57BL; Oligodeoxyribonucleotides; Ovalbumin; Th1 Cells

Warifteine is a bisbenzylisoquinoline alkaloid isolated from the Cissampelos sympodialis Eichl (Menispermaceae). This plant is used in the folk medicine for the treatment of airway respiratory diseases. A murine model of immediate allergic reaction was used to evaluate warifteine treatment in the IgE production, leukocyte activation, thermal hyperalgesia, mast cell degranulation and scratching behavior. BALB/c mice treated with warifteine (0.4-10 mg/Kg) 1 h before OVA sensitization reduced OVA induced paw edema as well as the OVA-specific IgE serum titers as compared with non-treated and OVA-sensitized animals. Warifteine also reduced the mice death evoked by IgE-dependent anaphylactic shock reaction at 30 min after intravenous OVA challenge. To assess the effect of warifteine treatment on T cell proliferative response, spleen cells from warifteine treated or non-treated and OVA-sensitized animals were evaluated. Spleen cells from warifteine treated animals (2.0 mg/kg) did not proliferate following OVA stimulation as compared with spleen cell cultures from non-treated animals. This response may be related with the increase of NO production as observed in peritoneal macrophage cultures treated with warifteine. Thermal hyperalgesia evoked by IgE or histamine/5-hydroxytryptamine challenge was inhibited on rats at dose of 4.0 mg/kg. Warifteine treatment (0.6 or 6.0 microg/ml) also decreased the IgEalphaDNP-BSA sensitized mast degranulation after DNP-BSA challenge measured by histamine release. In addition, compound 48/80-induced scratching behavior was also sensitive to warifteine treatment. These results demonstrate for the first time that warifteine treatment reduced the allergy-associated responses.

Topics: Alkaloids; Anaphylaxis; Animals; Cell Degranulation; Cell Proliferation; Drug Evaluation, Preclinical; Histamine Release; Hyperalgesia; Hypersensitivity, Immediate; Immunoglobulin E; Lymphocyte Activation; Macrophages, Peritoneal; Mast Cells; Mice; Mice, Inbred BALB C; Nitric Oxide; Ovalbumin; Rats; Rats, Wistar; T-Lymphocytes

Anaphylaxis is an acute, severe, and potentially fatal systemic allergic reaction. Immunoglobulin E (IgE), mast cells, and histamine have long been associated with anaphylaxis, but an alternative pathway mediated by IgG has been suggested to be more important in the elicitation of anaphylaxis. Here, we showed that basophils, the least common blood cells, were dispensable for IgE-mediated anaphylaxis but played a critical role in IgG-mediated, passive and active systemic anaphylaxis in mice. In vivo depletion of basophils but not macrophages, neutrophils, or NK cells ameliorated IgG-mediated passive anaphylaxis and rescued mice from death in active anaphylaxis. Upon capture of IgG-allergen complexes, basophils released platelet-activating factor (PAF), leading to increased vascular permeability. These results highlight a pivotal role for basophils in vivo and contrast two major, distinct pathways leading to allergen-induced systemic anaphylaxis: one mediated by basophils, IgG, and PAF and the other "classical" pathway mediated by mast cells, IgE, and histamine.

Topics: Allergens; Anaphylaxis; Animals; Basophils; Immunoglobulin E; Immunoglobulin G; Macrophages; Mast Cells; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Mice, Transgenic; Ovalbumin; Platelet Activating Factor; Receptors, IgG; Signal Transduction

Previous mouse and clinical studies demonstrate a link between Th2 intestinal inflammation and induction of the effector phase of food allergy. However, the mechanism by which sensitization and mast cell responses occurs is largely unknown. We demonstrate that interleukin (IL)-9 has an important role in this process. IL-9-deficient mice fail to develop experimental oral antigen-induced intestinal anaphylaxis, and intestinal IL-9 overexpression induces an intestinal anaphylaxis phenotype (intestinal mastocytosis, intestinal permeability, and intravascular leakage). In addition, intestinal IL-9 overexpression predisposes to oral antigen sensitization, which requires mast cells and increased intestinal permeability. These observations demonstrate a central role for IL-9 and mast cells in experimental intestinal permeability in oral antigen sensitization and suggest that IL-9-mediated mast cell responses have an important role in food allergy.

Topics: Administration, Oral; Anaphylaxis; Animals; Antigens; Cromolyn Sodium; Disease Susceptibility; Fatty Acid-Binding Proteins; Gene Expression Profiling; Hypersensitivity; Interleukin-9; Intestines; Mast Cells; Mastocytosis; Mice; Mice, Transgenic; Ovalbumin; Permeability; Phenotype; Rats; Receptors, Interleukin-4; STAT6 Transcription Factor; Th2 Cells

It remains unclear whether lipopolysaccharide (LPS) pre-treatment, which prevents Th2-type responses via Toll-like receptor 4 (TLR4), inhibits anaphylaxis. To determine the dose-dependent effects of LPS pre-treatment on anaphylactic decreases in rectal temperature caused by ovalbumin (OVA) re-exposure in immunized mice, C3H/HeN mice were divided into vehicle/OVA (0 mg/kg LPS), L-LPS/OVA (0.5 mg/kg LPS), M-LPS/OVA (1.0 mg/kg LPS) and H-LPS/OVA (3.0 mg/kg LPS) groups. After receiving these treatments, the mice were systemically immunized with OVA. Negative control mice were not immunized with OVA (N-OVA). After measuring the serum levels of OVA-specific IgE and IgG1 antibodies, the mice were examined for changes in their rectal temperature and plasma histamine concentration after OVA re-exposure. The allergen-specific IgE and IgG1 concentrations in sera from L-LPS/OVA, M-LPS/OVA and H-LPS/OVA mice were significantly lower than those in sera from vehicle/OVA mice despite OVA immunization. However, the antibody levels in all OVA-immunized mice, with the exception of the IgG1 levels in H-LPS/OVA mice, were significantly higher than those in N-OVA mice. Interestingly, H-LPS/OVA mice were the only group that did not exhibit a decrease in rectal temperature, since the rectal temperatures in vehicle/OVA, L-LPS/OVA and M-LPS/OVA mice were significantly decreased by OVA re-exposure. Furthermore, the decrease in rectal temperature after OVA re-exposure in L-LPS/OVA mice, which did not exhibit an increase in the plasma histamine concentration, was significantly prevented by treatment with a platelet-activating factor (PAF) receptor antagonist alone. Taken together, the present results indicate that high-dose LPS pre-treatment may prevent anaphylaxis in OVA-immunized mice, and that this mechanism may depend on inhibition of the IgG-PAF pathway rather than the IgE-histamine pathway.

Topics: Allergens; Anaphylaxis; Animals; Antibody Formation; Body Temperature; Histamine; Immunization; Immunoglobulin E; Immunoglobulin G; Lipopolysaccharides; Male; Mice; Ovalbumin; Platelet Activating Factor; Rectum

Various inflammatory mediators released from antigen-activated mast cells are considered to play a key role in the pathogenesis of food allergy. The aim of the present study was to determine the mechanisms underlying the antigen-induced anaphylactic responses in the rat colons. Wistar rats were sensitized by intraperitoneal injection of ovalbumin (OVA). The contractilities of isolated proximal colons of the sensitized rats were studied in the organ bath. OVA challenges of sensitized tissues induced prolonged contractile responses. The antigen-induced contractions were greatly reduced by mast cell stabilizer doxantrazole (10 microM). However, the contractions were resistant to histamine H1 receptor antagonist and prostaglandin D2 receptor antagonist. In contrast, non-selective cyclooxygenase (COX) inhibitor indomethacin (1 microM) significantly reduced the contractions by 61.0%. Furthermore, selective COX-1 inhibitor FR122047 (10 microM) as well as selective COX-2 inhibitor NS-398 (10 microM) significantly inhibited the contractions by 50.1% and 50.3%, respectively. Nevertheless, the transcript levels of COX-2 as well as COX-1 were not upregulated by OVA in the proximal colons of the sensitized rats. The present results indicate that de novo arachidonic acid metabolites synthesis by constitutive COX-1 as well as constitutive COX-2 within mast cells contribute to the altered smooth muscle contractilities in the colons under the anaphylactic condition.

Topics: Anaphylaxis; Animals; Chronic Disease; Colon; Cyclooxygenase 1; Cyclooxygenase 2; Intestinal Mucosa; Male; Mast Cells; Muscle Contraction; Muscle, Smooth; Ovalbumin; Rats; Rats, Wistar

Although immunotherapy has been reported as the only treatment able to revert the T-helper type 2 (Th2) response, its administration has some disadvantages such as the requirement of multiple doses, possible side-effects provoked by conventional adjuvants and the risk of suffering an anaphylactic shock. For these reasons, drug-delivery systems appear to be a promising strategy due to its ability to (i) transport the allergens, (ii) protect them from degradation, (iii) decrease the number of administrations and (iv) act as immuno-adjuvants.. The aim of this work was to evaluate the properties of poly-epsilon-caprolactone (PCL) microparticles as adjuvants in immunotherapy using ovalbumin (OVA) as an allergen model. For this purpose, the protection capacity of these microparticles (OVA PCL) against OVA allergy was studied in a murine model.. The humoral and cellular-induced immune response generated by OVA encapsulated into PCL microparticles was studied by immunizing BALB/c mice intradermically. Also, OVA-sensitized mice were treated with OVA PCL and OVA adsorbed to aluminium hydroxide (OVA-Alum). Fifteen days after therapy, animals were challenged with OVA and different signs of anaphylactic shock were evaluated.. One single shot by an intradermal route with OVA PCL resulted in a Th2-type immune response. In OVA-sensitized mice, treatment with OVA PCL elicited high OVA-specific IgG but low levels of IgE. Furthermore, OVA PCL mice group displayed lower levels of serum histamine and higher survival rate in comparison with the positive control group.. The anaphylactic shock suffered by OVA PCL-treated mice was weaker than the one induced in the OVA-Alum group. Hence, the intradermal immunization with OVA PCL microparticles induced hyposensitization in OVA-allergic mice.

Topics: Allergens; Anaphylaxis; Animals; Drug Administration Routes; Humans; Immune Tolerance; Mice; Ovalbumin; Th2 Cells

Experimental airway allergy in mice leads to increased activity in specific hypothalamic and amygdaloid nuclei, and behavioral changes. The experiments described here were designed to determine the role of anaphylactic antibodies, mast cell degranulation, and lung inflammation in the neural and behavioral correlates of an experimental murine asthma-like response. Animals were sensitized intraperitoneally with ovalbumin adsorbed to alum, and challenged by intranasal ovalbumin instillation or aerosol. To induce immunological tolerance, animals were fed ovalbumin in the drinking water for 5 consecutive days, along with primary sensitization. Depletion of IgE was also accomplished with a non-anaphylactic anti-IgE antibody. Mast cell degranulation was inhibited by cromolyn. In addition to BALB/c animals, C3H/HeJ mice were used for their relative resistance to lung allergic inflammation. We confirmed that ovalbumin challenge in allergic mice leads to increased activity in the paraventricular nucleus of the hypothalamus and central nucleus of the amygdala, and avoidance behavior towards an allergen-associated compartment. Moreover, these responses were precluded by oral tolerance or anti-IgE treatment, even in the presence of IgG1. Cromolyn abrogates both responses in the presence of anaphylactic antibodies. Finally, although sensitized C3H/HeJ mice did not develop airway inflammation, they exhibited brain and behavioral changes similar to BALB/c animals. The repercussions of murine allergic asthma on brain and behavior are IgE-dependent, mediated by mast cell degranulation, and do not require a pulmonary inflammatory infiltrate, suggesting that the early phase of this immediate allergic response suffices for the brain activation associated with avoidance behavior towards exposure to the allergen.

Topics: Amygdala; Analysis of Variance; Anaphylaxis; Animals; Asthma; Avoidance Learning; Behavior, Animal; Cell Degranulation; Disease Models, Animal; Hypersensitivity; Immune Tolerance; Immunoglobulin E; Male; Mast Cells; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Neuroimmunomodulation; Ovalbumin; Paraventricular Hypothalamic Nucleus; Species Specificity; Statistics, Nonparametric

The objective of this study is to evaluate the activity of a novel peptide, i.e., bifunctional peptide inhibitor (BPI), which targets the immunological synapse and inhibits autoimmune responses in an antigen-specific manner. Proteolipid protein (PLP)-BPI was designed by conjugating two peptides, an encephalitogenic epitope of proteolipid protein (PLP(139-151)) and an intercellular adhesion molecule-1-binding peptide derived from alpha(L) integrin (CD11a(237-246)), via a spacer peptide. The therapeutic effect of PLP-BPI was studied in experimental autoimmune encephalomyelitis (EAE) in female SJL/J mice as a model for human multiple sclerosis. Mice that received i.v. injections of PLP-BPI showed significantly lower EAE disease scores and incidence than those treated with vehicle, PLP(139-151) peptide only, CD11a(237-246) peptide only, unlinked mixture of PLP(139-151), and CD11a(237-246) peptides, or other control peptides. Multiple injections of antigenic peptide can produce anaphylactic responses; interestingly, PLP-BPI-treated animals have significantly lower anaphylactic response than do the PLP(139-151)-treated group. Therefore, PLP-BPI can effectively inhibit the disease severity and incidence of EAE with a lower possibility of inducing fatal anaphylaxis. These results suggest that BPI-type molecules can be used to treat different autoimmune diseases in which antigenic epitopes have been identified.

Topics: Amino Acid Sequence; Anaphylaxis; Animals; Antigens; Body Weight; Capsid Proteins; CD11a Antigen; Encephalomyelitis, Autoimmune, Experimental; Female; Interferon-gamma; Interleukin-10; Interleukin-4; Mice; Mice, Inbred Strains; Models, Immunological; Molecular Sequence Data; Myelin Proteolipid Protein; Ovalbumin; Peptide Fragments; Peptides; Spleen; T-Lymphocyte Subsets; T-Lymphocytes, Regulatory; Time Factors; Transforming Growth Factor beta; Vaccination

Microbial infection is thought to modulate allergic disorders, and we previously demonstrated that not only mast cells (which release histamine), but also platelets are involved in the anaphylaxis induced in mice sensitised to ovalbumin (OVA). Here, we examined the effects of a lipopolysaccharide (LPS) from the oral bacterium Prevotella intermedia (Pi) on OVA-induced anaphylaxis. Upon intraperitoneal co-injection of Pi-LPS plus OVA into BALB/c mice, the Pi-LPS displayed a potent adjuvant effect comparable to that of alum (a standard adjuvant) in terms of its abilities to induce both anaphylactic shock and histamine-release following an antigen (OVA)-challenge. Moreover, an injection of Pi-LPS given to OVA+alum-sensitised mice shortly before an OVA-challenge augmented the shock-response. This LPS-pretreatment did not affect histamine-release, but did augment pulmonary platelet accumulation. Histamine was not by itself causal for shock-induction in sensitised mice. These results suggest that oral bacteria and/or their constituents (such as LPS) may help to sensitise the host to an antigen or exacerbate the host's allergic reactions ("aggravation effect"), probably by enhancing the platelet response to the antigen OVA.

Topics: Anaphylaxis; Animals; Antibodies, Monoclonal; Antigens, Differentiation; Blood Platelets; Female; Histamine; Histamine Release; Lipopolysaccharides; Mice; Mice, Inbred BALB C; Ovalbumin; Prevotella intermedia

Food allergies have become increasingly prevalent during the past few decades. Diarrhea is one of the most frequent intestinal symptoms caused by food allergens and is characterized by imbalanced ion exchange and water transfer; however, the underlying mechanism of allergic diarrhea remains unclear. Water transfer across the intestinal epithelial membrane seems to occur via aquaporins (AQPs). However, the molecular mechanism of water transfer and the pathophysiological roles of aquaporins in the intestine have not been fully established. The present studies have focused on the alterations of AQPs in a mouse model of allergic diarrhea in which BALB/c mice developed diarrhea following repeated challenges of orally administered ovalbumin. Quantitative real-time PCR analysis and immunohistochemical technique were used for expression of mRNA and protein of AQPs, respectively. AQP4 and AQP8 mRNA levels were significantly decreased in the proximal colon of allergic mice compared to controls; likewise, expression of AQP4 and AQP8 proteins was reduced in the proximal colon of the allergic mice. These results suggest that allergic diarrhea is associated with a downregulation in AQP4 and AQP8 expression.

Topics: Anaphylaxis; Animals; Aquaporin 4; Aquaporins; Colon; Diarrhea; Down-Regulation; Food Hypersensitivity; Immunohistochemistry; Injections, Intraperitoneal; Male; Mice; Mice, Inbred BALB C; Ovalbumin; RNA, Messenger

The aim of this study was to investigate the adjuvant properties of oral-administered Gantrez AN nanoparticles with ovalbumin (as allergen model) and, in some cases, lipopolysaccharide of Brucella ovis as immunomodulator. For this purpose, BALB/c mice were administered by oral gavage with OVA nanoparticles and both Th1 and Th2 markers (IgG2a and IgG1, respectively) were enhanced. On the other hand, these carriers administered by oral route were able to protect a model of sensitized mice to ovalbumin from anaphylactic shock. These results are highly suggestive for the valuable use of Gantrez nanoparticles in oral immunotherapy with allergens.

Topics: Adjuvants, Immunologic; Administration, Oral; Allergens; Anaphylaxis; Animals; Brucella ovis; Disease Models, Animal; Female; Immunoglobulin G; Immunotherapy; Maleates; Mice; Mice, Inbred BALB C; Nanoparticles; Ovalbumin; Polysaccharides, Bacterial; Polyvinyls

To clarify the role of NO in mouse anaphylactic hypotension, effects of a nitric oxide (NO) synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), on antigen-induced hypotension and portal hypertension were determined in anesthetized BALB/c mice. Systemic arterial pressure (Psa), central venous pressure (Pcv), and portal venous pressure (Ppv) were directly and simultaneously measured. Mice were first sensitized with ovalbumin, and then the injection of antigen was used to decrease Psa and increase Ppv. Pretreatment with L-NAME (1 mg/kg) attenuated this antigen-induced systemic hypotension, but not the increase in Ppv. The effect of inhibitors of soluble guanylate cyclase on anaphylactic hypotension were studied with either methylene blue (3.0 mg/kg) or 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (10 mg/kg). Neither modulated any antigen-induced changes. Furthermore, methylene blue did not improve systemic hypotension induced by Compound 48/80 (4.5 mg/kg), a mast cell degranulator, which can produce non-immunological anaphylactoid reactions. These data show in anesthetized BALB/c mice that L-NAME attenuated anaphylactic hypotension without affecting portal hypertension. This beneficial effect of L-NAME appears not to depend on the soluble guanylate cyclase pathway.

Topics: Anaphylaxis; Anesthesia; Animals; Blood Pressure; Enzyme Inhibitors; Guanylate Cyclase; Hypertension; Liver Circulation; Male; Methylene Blue; Mice; Mice, Inbred BALB C; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase Type III; Ovalbumin; Oxadiazoles; Quinoxalines

The present study investigated the acute inflammatory response (increase in vascular permeability and leukocytes migration) in the pleura of spontaneously hypertensive rats (SHR) and normotensive rats (NTR), using two different stimulus: carrageenan and active anaphylaxis. In addition, the role of endogenous nitric oxide in these responses was investigated.. The inflammatory response induced by intrapleural carrageenan injection in SHR developed similarly to that in NTR. Treatment with L-NAME, reduced the intensity of this response in both groups of rats. The inflammatory response induced by active anaphylaxis in SHR and NTR was different. The increase in vascular permeability occurred later in the SHR compared to NTR. The number of leukocyte present in inflammatory exudates was increased at 4 h in both groups of rats. L-NAME treatment did not inhibit exudation at the intervals under analysis, however, reduced the number of mononuclear cells in the inflammatory exudate of SHR.. The development of the inflammatory response in SHR differs from that in NTR, depending on the nature of the inflammatory stimulus. Endogenous NO plays a clear role in carrageenan-induced inflamma-tion, but not in immunologically mediated inflammation in the analyzed period.

Topics: Anaphylaxis; Animals; Capillary Permeability; Carrageenan; Cell Migration Assays, Leukocyte; Chemotaxis, Leukocyte; Disease Models, Animal; Enzyme Inhibitors; Exudates and Transudates; Hypertension; Leukocytes; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase; Ovalbumin; Pleurisy; Rats; Rats, Inbred SHR; Rats, Wistar

Hepatic anaphylactic venoconstriction is partly involved in anaphylactic hypotension. We determined the chemical mediators responsible for anaphylaxis-induced segmental venoconstriction in perfused livers isolated from ovalbumin-sensitized rats. Livers were perfused portally and recirculatingly at constant flow with diluted blood. The portal venous pressure (Ppv), hepatic venous pressure (Phv), liver weight and hepatic oxygen consumption were continuously measured. The sinusoidal pressure was measured by the double occlusion pressure (Pdo), and was used to determine the pre-sinusoidal (Rpre) and post-sinusoidal (Rpost) resistances. After antigen injection, both Ppv and Pdo increased, resulting in 5.6- and 1.6-fold increases in Rpre and Rpost, respectively. Liver weight showed a biphasic change of an initial decrease followed by an increase. Hepatic oxygen consumption significantly decreased after antigen. Anaphylaxis-induced increase in Rpre was most extensively inhibited by 38.6% by pretreatment with ONO-1078 (100 microM, a cysteinyl leukotriene receptor-1 antagonist), among all antagonists or inhibitors administrated individually including TCV-309 (20 microM), AA-2414 (10 microM), ketanserin (10 microM) and indomethacin (10 microM). Combined pretreatment with indomethacin and ONO-1078 exerted additive inhibitory effects and attenuated Rpre by 65.8%. However, TCV-309, a platelet activating factor (PAF) receptor antagonist, did not affect the anaphylactic response. In contrast, anaphylaxis-induced increase in Rpost was attenuated only by ONO-1078 combined pretreatment. The antigen-induced changes in liver weight and hepatic oxygen consumption were attenuated significantly when hepatic venoconstriction was attenuated. It is concluded that cysteinyl leukotrienes and cyclooxygenase products, but not PAF, are mainly involved in anaphylaxis-induced pre-sinusoidal constriction in isolated perfused rat livers.

Topics: Anaphylaxis; Animals; Antigens; Chromones; Cyclooxygenase Inhibitors; In Vitro Techniques; Indomethacin; Leukotriene Antagonists; Leukotrienes; Liver; Male; Organ Size; Ovalbumin; Oxygen Consumption; Prostaglandin-Endoperoxide Synthases; Rats; Rats, Sprague-Dawley; Vascular Resistance; Vasoconstriction; Venous Pressure

IL-4Ralpha-mediated STAT6 activation serves an essential role in various animal models of allergy and asthma at both the sensitization and effector phases. IL-4 and IL-13 signaling via the IL-4Ralpha chain exacerbates murine anaphylaxis, but the cell-specific requirements for IL-4Ralpha expression are unclear. The purpose of this study was to elucidate the mechanisms of systemic anaphylaxis to OVA in gene-targeted mice with a deletion of the IL-4Ralpha chain in the macrophage/neutrophil or CD4+ T lymphocyte population. Results demonstrated that anaphylaxis in this model was entirely dependent upon the FcgammaRII/III and was associated with mast cell degranulation. Expression of the IL-4Ralpha on CD4+ T cells, but not macrophages or neutrophils, was critical for severe anaphylaxis, characterized by diarrhea, hypothermia, and death. Ab depletion experiments demonstrated that IFN-gamma protected against mortality and severe intestinal pathology despite the presence of Ag and specific Ab. This protection was associated with reduced levels of mast cell protease, a marker of mast cell degranulation, suggesting that IFN-gamma may inhibit mast cell degranulation in vivo. These data suggest that it may be possible to limit the severity of anaphylaxis using rational therapies designed to increase numbers of IFN-gamma-producing cells by targeting IL-4Ralpha signaling in CD4+ T lymphocytes.

Topics: Anaphylaxis; Animals; Antibodies; Antigens, CD; CD4-Positive T-Lymphocytes; Cell Degranulation; Cytokines; Gene Deletion; Interferon-gamma; Interleukin-4 Receptor alpha Subunit; Mast Cells; Mice; Mice, Mutant Strains; Ovalbumin; Receptors, IgG

The granule-derived mouse mast cell proteases-1 and -2 (mMCP-1 and -2) colocalize in similar quantities in mucosal mast cells but micrograms of mMCP-1 compared with nanograms of mMCP-2 are detected in peripheral blood during intestinal nematode infection. This differential systemic response was investigated both in vitro and in vivo. Bone marrow-derived mucosal mast cell homologs released similar quantities of mMCP-1 and-2 concomitantly with beta-hexosaminidase in response to calcium ionophore ( approximately 60% release) or IgE/DNP (25% release). In contrast, serum from mice sensitized by infection with Nippostrongylus brasiliensis 10 days earlier contained >1500-fold more mMCP-1 (10,130 +/- 1,609 ng/ml) than mMCP-2 (6.4 +/- 1 ng/ml), but, in gut lumen, the difference was approximately 8-fold. After OVA sensitization, >600-fold more mMCP-1 (7,861 +/- 2,209 ng/ml) than mMCP-2 (12.8 +/- 4.7 ng/ml) was present in blood 1 h after challenge, but, in gut lumen, there were relatively comparable levels of mMCP-1 and -2. To estimate the rates of systemic accumulation and clearance, 10 microg of mMCP-1 or -2 was injected i.p. Plasma levels of injected mMCP-2 peaked (1%) at 15 min then declined, whereas levels of mMCP-1 were maximal (approximately 25%) at 3 h. Inactivation of mMCP-1 with PMSF before injection resulted in mMCP-2-like kinetics, but inhibition of mMCP-1 by serum gave kinetics similar to that of native mMCP-1. mMCP-1 isolated from serum is complexed with serpins and we conclude that both the accumulation and the longevity of mMCP-1 in blood is due to complex formation, protecting it from a pathway that rapidly clears mMCP-2, which is unable to form complexes with serpins.

Topics: Anaphylaxis; Animals; Cell Degranulation; Cells, Cultured; Chymases; Immunization; Intestinal Mucosa; Kinetics; Mast Cells; Mice; Mice, Inbred BALB C; Multiprotein Complexes; Nippostrongylus; Ovalbumin; Serine Endopeptidases; Serpins; Strongylida Infections

Mucosal tolerance can be induced by oral or nasal administration of soluble proteins and results in the suppression of cellular and/or humoral immune responses to the specific antigen.. To compare the effect of oral or nasal ovalbumin administration before, during or after immunization on the development of cellular and humoral immune responses by using a murine asthma model.. To induce lung allergic inflammation, animals were immunized twice with ovalbumin/aluminum hydroxide gel and challenged twice with ovalbumin. To induce tolerance, BALB/c mice received ovalbumin by the oral or nasal routes for 3 consecutive days. The ovalbumin administration was initiated before (day -7), during (day 0), or after immunization (day 7).. Airway eosinophilia, airway hyperreactivity, mucus hypersecretion, and cytokine production were suppressed when oral or nasal ovalbumin administration was initiated before immunization. Oral but not nasal ovalbumin exposure suppressed ovalbumin-specific nonanaphylactic IgG(1) antibodies, whereas both routes suppressed the production of anaphylactic IgG(1) and IgE antibodies. Mucosal ovalbumin administration at day 0 inhibited all T(H)2-mediated allergic parameters but not nonanaphylactic IgG(1) antibodies. Finally, ovalbumin exposure 7 days after immunization was still effective in suppressing lung allergy but not ovalbumin-specific anaphylactic IgG(1) and IgE antibodies.. We show that the effectiveness of mucosal tolerance depends on route and time and presents a hierarchical pattern of suppression in the following order: lung allergic responses > anaphylactic antibodies > ovalbumin-specific IgG(1).

Topics: Administration, Intranasal; Administration, Oral; Anaphylaxis; Animals; Asthma; Bronchial Hyperreactivity; Bronchoalveolar Lavage Fluid; Disease Models, Animal; Immune Tolerance; Immunization; Immunoglobulin E; Immunoglobulin G; Male; Mice; Mice, Inbred BALB C; Mucous Membrane; Ovalbumin; Pulmonary Eosinophilia; Time Factors

We often eat heat-coagulated (H-C) food proteins, but there have been few studies on the allergenic activity of H-C proteins after digestion and absorption in vivo. To show that H-C protein is not an allergen after digestion, mice were used to investigate the digestion and absorption of the protein through the intestinal epithelium into portal blood employing immunoblotting and competitive inhibition ELISA. Ovalbumin (OVA) was used as the model protein, and H-C OVA was prepared by heating a 5% OVA solution for 15 min in boiling water. Antigenic OVA was not detected in the soluble fraction of gastrointestinal contents or the portal blood of mice administered H-C OVA. Also, voluntary physical activities, as an assessment of anaphylaxis, were monitored for 15 h using OVA sensitized mice. Compared to the voluntary physical activities of sensitized mice without any load, no decrease in activity was observed in the group administered H-C OVA, but a significant decrease in activity was found in the mice administered unheated OVA. These results strongly indicate that H-C OVA does not retain allergenic properties.

Topics: Allergens; Anaphylaxis; Animals; Chickens; Digestion; Female; Gastric Mucosa; Hot Temperature; Immunoglobulin E; Intestinal Absorption; Intestine, Small; Mice; Mice, Inbred BALB C; Ovalbumin; Protein Denaturation; Running; Solubility

An influense was studied in rats of selenium enriched phycocyanin (Se-PC) from food microalgae Spirulina on anaphylactic reaction severity and circulating antibody response against model allergen--hen's egg white ovalbumin. Se-PC was introduced into diet in form of protein isolate precipitated with ammonia sulphate. Se-PC dosage made up to 450 mcg per rat daily that corresponded to 5 mcg of selenium. There were no differences revealed between experimental and control group that received standard diet in severity of anaphylactic reaction. Nevertheless rats receiving Se-PC demonstrated significantly increased specific IgG response. The probable immunomodulating properties of Se-PC included into food are discussed.

Topics: Anaphylaxis; Animals; Dietary Supplements; Egg Proteins, Dietary; Immunologic Factors; Male; Ovalbumin; Phycocyanin; Rats; Rats, Wistar; Selenium Compounds

Systemic anaphylaxis is the most severe form of immediate hypersensitivity reaction. The activation of the complement system occurs during anaphylactic shock. The purpose of this study was to determine in a mouse model whether the lectin pathway of complement activation is involved in anaphylaxis.. To see whether the lectin pathway is involved in anaphylactic shock, serum mannan-binding lectin (MBL) levels were measured after passive anaphylaxis. Also MBL expression and binding to potential ligands were investigated. To determine whether complement or mast cell activation is essential for hypothermia in anaphylactic shock, mouse strains deficient in MBL-A and MBL-C, C1q, factors B and C2, C5, C5aR, or mast cells were tested.. After antigenic challenge a marked drop in body temperature as well as a rapid decrease in serum MBL levels were observed. The decrease of serum MBL levels in shock could not be attributed to MBL binding to immune complexes or tissues, but an interaction of MBL with mast cell-derived proteoglycans was seen. In contrast to mast cell-deficient mice, none of the complement-deficient mouse strains were protected from shock-associated hypothermia.. These results indicate that neither MBL nor activation of the complement cascade is crucial for the induction of anaphylaxis. In contrast mast cell activation is associated with the development of hypothermia and possibly the observed decrease in serum MBL levels.

Topics: Anaphylaxis; Animals; Complement Activation; Enzyme-Linked Immunosorbent Assay; Female; Hypothermia; Immunohistochemistry; Mannose-Binding Lectin; Mast Cells; Mice; Mice, Inbred DBA; Mice, Mutant Strains; Ovalbumin; Polymerase Chain Reaction; Proteoglycans; RNA, Messenger

A genetic contribution to asthma susceptibility is well recognized, and linkage studies have identified a large number of genes associated with asthma pathogenesis. Recently, a locus encoding a seven-transmembrane protein was shown to be associated with asthma in founder populations. The expression of the protein GPRA (G protein-coupled receptor for asthma susceptibility) in human airway epithelia and smooth muscle, and its increased expression in a mouse model of asthma, suggested that a gain-of-function mutation in this gene increased the disease risk. However, we report here that the development of allergic lung disease in GPRA-deficient mice is unaltered. A possible explanation for this finding became apparent upon reexamination of the expression of this gene. In contrast to initial studies, our analyses failed to detect expression of GPRA in human lung tissue or in mice with allergic lung disease. We identify a single parameter that distinguishes GPRA-deficient and wild-type mice. Whereas the change in airway resistance in response to methacholine was identical in control and GPRA-deficient mice, the mutant animals showed an attenuated response to thromboxane, a cholinergic receptor-dependent bronchoconstricting agent. Together, our studies fail to support a direct contribution of GPRA to asthma pathogenesis. However, our data suggest that GPRA may contribute to the asthmatic phenotype by altering the activity of other pathways, such as neurally mediated mechanisms, that contribute to disease. This interpretation is supported by high levels of GPRA expression in the brain and its recent identification as the neuropeptide S receptor.

Topics: Acute Disease; Anaphylaxis; Animals; Asthma; Bronchoconstrictor Agents; Disease Models, Animal; Gene Expression; Humans; Hypothalamus; Lipopolysaccharides; Lung; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Mutant Strains; Muscle, Smooth; Ovalbumin; Phenotype; Pneumonia; Receptors, G-Protein-Coupled; Respiratory Mechanics; Retina

Effects of hematocrit (Hct) on N-nitro-L-arginine methyl ester (L-NAME)-induced modulation of anaphylactic venoconstriction were determined in isolated perfused rat livers. The rats were sensitized with ovalbumin (1 mg), and the livers were excised 2 weeks later and perfused portally and recirculatingly under constant flow at Hct of 0%, 5%, 16%, and 22%. The hepatic sinusoidal pressure was estimated via the double occlusion pressure (Pdo), and the presinusoidal resistance (Rpre) and the postsinusoidal resistance (Rhv) were calculated. The antigen of ovalbumin 0.1 mg was injected into the reservoir at 10 minutes after pretreatment with L-NAME (100 microM) or D-NAME (100 microM). Perfusate viscosity, a determinant of vascular resistance and shear stress, was increased in parallel with Hct. In the D-NAME groups, antigen caused predominant presinusoidal constriction. The magnitude of venoconstriction was significantly smaller at Hct 0% than at Hct 5% to 22%, whereas no significant differences were found among Hct 5% to 22%. L-NAME potentiated the antigen-induced increase in Rpre, but not in Rpost at Hct 5% to 22% as compared with D-NAME. But the augmentative effects of L-NAME were similar in magnitude among Hct 5% to 22%. These findings suggest that hepatic anaphylaxis increases production of nitric oxide, which consequently attenuates anaphylactic presinusoidal constriction in rat livers, and that these effects are independent of perfusate Hct or viscosity in blood-perfused rat livers.

Topics: Anaphylaxis; Animals; Drug Synergism; Enzyme Inhibitors; Hematocrit; Liver; Liver Circulation; Male; NG-Nitroarginine Methyl Ester; Ovalbumin; Perfusion; Portal Pressure; Rats; Rats, Sprague-Dawley; Stereoisomerism; Vascular Resistance; Vasoconstriction; Viscosity

1. The effects of the nitric oxide (NO) synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) on anaphylaxis-induced venoconstriction were examined in rat isolated livers perfused with blood-free solutions in order to clarify the role of NO in anaphylactic venoconstriction. 2. Rats were sensitized with ovalbumin (1 mg) and, 2 weeks later, livers were excised and perfused portally in a recirculating manner at a constant flow with Krebs'-Henseleit solution. The antigen (ovalbumin; 0.1 mg) was injected into the reservoir 10 min after pretreatment with L-NAME (100 micromol/L) or D-NAME (100 micromol/L) and changes in portal vein pressure (Ppv), hepatic vein pressure (Phv) and perfusate flow were monitored. In addition, concentrations of the stable metabolites of NO ( and ) were determined in the perfusate using an HPLC-Griess system. 3. The antigen caused hepatic venoconstriction, as evidenced by an increase in Ppv from a mean (SEM) baseline value of 7.7 +/- 0.1 cmH2O to a peak of 21.4 +/- 1.1 cmH2O at 3 min in D-NAME-pretreated livers. Pretreatment with L-NAME augmented anaphylactic venoconstriction, as reflected by a higher Ppv (27.4 +/- 0.8 cmH2O) after antigen than observed following D-NAME pretreatment. The addition of L-arginine, a precursor for the synthesis of NO, reversed the augmentation of anaphylactic venoconstricion by L-NAME. This suggests that hepatic anaphylaxis increased the production of NO, which consequently attenuated anaphylactic venoconstriction. However, perfusate NOx levels did not increase significantly after antigen in livers pretreated with either L-NAME or D-NAME. 4. In conclusion, L-NAME potentiates rat anaphylactic hepatic venoconstriction, suggesting that NO contributes to the attenuation of the venoconstriction. However, this functional evidence was not accompanied by corresponding changes in perfusate NOx concentrations.

Topics: Anaphylaxis; Animals; Arginine; Liver; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide; Ovalbumin; Rats; Rats, Sprague-Dawley; Vasoconstriction

To study the effects of ketotifen fumarate, olopatadine, and levocabastine on ocular active anaphylaxis in guinea pigs and on ocular immediate hypersensitivity in albino rats.. Clinical grading scores and Evans blue dye leakage to eyelids and to eyeballs were assessed in five treatment groups (n = 10): ketotifen fumarate 0.025%, olopatadine 0.1%, levocabastine 0.05%, negative control, and positive control.. At 20 minutes after challenge, edema scores for ketotifen-treated guinea pigs were statistically significantly lower than those for levocabastine or olopatadine. Active treatment significantly reduced vascular leakage in both models. Ketotifen significantly reduced vascular leakage in eyelids compared with the other drugs. In guinea pigs, vascular leakage in eyeballs was significantly reduced with ketotifen fumarate compared with olopatadine and levocabastine.. In the guinea pig model, ketotifen was more effective than olopatadine and levocabastine at reducing conjunctival edema and vascular permeability in eyelids and eyeballs. In the rat model, ketotifen was more effective at reducing vascular permeability in eyelids than olopatadine and levocabastine.

Topics: Anaphylaxis; Animals; Capillary Permeability; Conjunctivitis, Allergic; Dibenzoxepins; Disease Models, Animal; Edema; Eyelids; Guinea Pigs; Histamine H1 Antagonists; Ketotifen; Male; Olopatadine Hydrochloride; Ophthalmic Solutions; Ovalbumin; Piperidines; Rats

1. The role of shear stress in nitric oxide (NO)-mediated attenuation of anaphylactic venoconstriction was studied using an isolated ovalbumin-sensitized guinea pig liver. 2. Guinea pigs were actively sensitized by a subcutaneous injection of 1 mg ovalbumin. Two weeks after sensitization, the livers were perfused with diluted blood under constant flow or constant perfusion pressure. The constant flow could result in increased shear stress during constriction, while the constant perfusion pressure could prevent changes in shear stress. Using the double occlusion technique to estimate the hepatic sinusoidal pressure, pre- and postsinusoidal constriction was evaluated. Hepatic anaphylaxis was induced by an injection of ovalbumin (4 microg) into the perfusate, the volume of which was 40 mL. 3. Under either constant flow or pressure, anaphylaxis caused venoconstriction of predominantly presinusoids over postsinusoids, although anaphylactic venoconstriction under constant pressure was significantly greater than that under constant flow. When shear stress was held constant by maintaining constant perfusion pressure, a NO synthase inhibitor, Nomega-nitro-L-arginine methyl ester (L-NAME, 100 micromol/L), potentiated similarly both pre- and postsinusoidal constriction induced by anaphylaxis. This suggests that hepatic anaphylaxis shear stress-independently generates NO, resulting in dilatation of both pre- and postsinusoidal vessels in a similar magnitude. In contrast, when shear stress was allowed to rise under constant flow, anaphylactic presinusoidal constriction was preferentially potentiated by L-NAME. 4. Hepatic anaphylaxis can increase NO production in a shear stress-independent manner and dilates similarly both pre- and postsinusoids, while NO produced in a shear stress-dependent manner attenuates predominantly venoconstriction of the presinusoids where shear stress is preferentially increased.

Topics: Anaphylaxis; Animals; Bile; Blood Flow Velocity; Blood Pressure; Enzyme Inhibitors; Guinea Pigs; Immunization; In Vitro Techniques; Liver; Liver Circulation; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase; Organ Size; Ovalbumin; Perfusion; Stereoisomerism; Stress, Mechanical; Vascular Resistance; Vasoconstriction

Some epidemiological or association studies suggest that transforming growth factor-beta (TGF-beta) in breast milk may be a decisive factor in diminishing the risk of allergic diseases during infancy. The observations have prompted us to investigate whether TGF-beta, when taken orally, can affect allergic immune responses. Repeated high-dose ovalbumin peptide (OVA) feeding was previously reported to induce OVA-specific IgE production and an anaphylactic reaction after intravenous challenge of OVA in OVA-TCR transgenic mice, which might represent a model for food allergy. By using this model, we showed here that oral administration of high-dose TGF-beta simultaneously with OVA feeding significantly inhibited the OVA-specific IgE elevation and anaphylactic reaction in OVA-TCR transgenic DO11.10 mice. These effects were associated with suppression of OVA-specific IL-4 production and GATA-3 expression and with up-regulation of IFN-gamma production and T-bet expression by splenocytes. Intra-peritoneal injection of anti-TGF-beta-neutralizing antibody abolished the inhibitory effects of orally administered TGF-beta on the serum IgE response and anaphylactic reaction after OVA feeding in DO11.10 mice. Interestingly, oral administration of high-dose TGF-beta suppressed activation-induced T cell death induced by OVA feeding in DO11.10 mice. We thus conclude that TGF-beta, when taken orally at high dose, has the capacity to modulate a food allergy-related reaction, at least in part, through its systemic activity.

Topics: Administration, Oral; Anaphylaxis; Animals; Antigens, Differentiation, T-Lymphocyte; Apoptosis; CD4-Positive T-Lymphocytes; Cytokines; Fas Ligand Protein; Food Hypersensitivity; Immunoglobulin E; Immunoglobulin G; Injections, Subcutaneous; Membrane Glycoproteins; Mice; Mice, Inbred BALB C; Mice, Transgenic; Ovalbumin; Spleen; T-Lymphocyte Subsets; Transforming Growth Factor beta; Tumor Necrosis Factors

We determined the roles of liver and splanchnic vascular bed in anaphylactic hypotension in anesthetized rats and the effects of anaphylaxis on hepatic vascular resistances and liver weight in isolated perfused rat livers. In anesthetized rats sensitized with ovalbumin (1 mg), an intravenous injection of 0.6 mg ovalbumin caused not only a decrease in systemic arterial pressure from 120 +/- 9 to 43 +/- 10 mmHg but also an increase in portal venous pressure that persisted for 20 min after the antigen injection (the portal hypertension phase). The elimination of the splanchnic vascular beds, by the occlusions of the celiac and mesenteric arteries, combined with total hepatectomy attenuated anaphylactic hypotension during the portal hypertension phase. For the isolated perfused rat liver experiment, the livers derived from sensitized rats were hemoperfused via the portal vein at a constant flow. Using the double-occlusion technique to estimate the hepatic sinusoidal pressure, presinusoidal (R(pre)) and postsinusoidal (R(post)) resistances were calculated. An injection of antigen (0.015 mg) caused venoconstriction characterized by an almost selective increase in R(pre) rather than R(post) and liver weight loss. Taken together, these results suggest that liver and splanchnic vascular beds are involved in anaphylactic hypotension presumably because of anaphylactic presinusoidal contraction-induced portal hypertension, which induced splanchnic congestion resulting in a decrease in circulating blood volume and thus systemic arterial hypotension.

Topics: Anaphylaxis; Anesthesia; Animals; Hypertension, Portal; Hypotension; Liver Circulation; Male; Ovalbumin; Rats; Rats, Sprague-Dawley; Splanchnic Circulation; Vascular Resistance; Vasoconstriction

Anaphylaxis represents an extreme form of allergic reaction, consisting of a sensitization phase during which allergen-specific IgE are produced and an acute effector phase triggered by allergen-induced degranulation of mast cells. We studied the role of IL-9, a Th2 cytokine implicated in asthma, in different models of murine anaphylaxis. Using a passive model of systemic anaphylaxis, in which anti-DNP IgE Abs were administered before challenge with DNP-BSA, we found that IL-9-transgenic mice or wild-type mice treated with IL-9 for 5 days were highly sensitive to fatal anaphylaxis. This effect was reproduced in both anaphylaxis-susceptible and -resistant backgrounds (FVB/N or [FVB/N x BALB/c] F(1) mice, respectively) and correlated with increased serum concentrations of mouse mast cell protease-1 level, a protein released upon mast cells degranulation. By contrast, IL-9 did not increase the susceptibility to passive cutaneous anaphylaxis. IL-9 expression also increased the susceptibility to fatal anaphylaxis when mice were sensitized by immunization against OVA before challenge with the same Ag. In this model, serum from sensitized, IL-9-transgenic mice was more potent in transferring susceptibility to OVA challenge into naive mice, indicating that IL-9 also promotes the sensitization stage. Finally, using IL-9R-deficient mice, we found that despite its anaphylaxis-promoting activity, IL-9 is dispensable for development of both passive and active anaphylaxis, at least in the C57BL/6 mouse background. Taken together, the data reported in this study indicate that IL-9 promotes systemic anaphylaxis reactions, acting at both the sensitization and effector stages, but is not absolutely required for this process.

Topics: Anaphylaxis; Animals; Chymases; Disease Models, Animal; Female; Immunization; Interleukin-9; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Ovalbumin; Passive Cutaneous Anaphylaxis; Receptors, Interleukin; Receptors, Interleukin-9; Serine Endopeptidases

The pathophysiology of the hepatic vascular response to anaphylaxis in guinea pig is not known. We studied effects of anaphylaxis on hepatic vascular resistances and liver weight in isolated perfused livers derived from guinea pigs sensitized with ovalbumin. We also determined whether nitric oxide (NO) or carbon monoxide (CO) modulates the hepatic anaphylaxis. The livers were perfused portally and recirculatingly at constant flow with diluted blood. With the use of the double-occlusion technique to estimate the hepatic sinusoidal pressure (Pdo), portal venous resistance (Rpv) and hepatic venous resistance (Rhv) were calculated. An antigen injection caused venoconstriction characterized by an increase in Rpv greater than Rhv and was accompanied by a large liver weight gain. Pretreatment with the NO synthase inhibitor NG-nitro-l-arginine methyl ester, but not the heme oxygenase inhibitor zinc protoporphyrin IX, potentiated the antigen-induced venoconstriction by increasing both Rpv and Rhv (2.2- and 1.2-fold increase, respectively). In conclusion, anaphylaxis causes both pre- and postsinusoidal constriction in isolated guinea pig livers. However, the increases in postsinusoidal resistance and Pdo cause hepatic congestion. Endogenously produced NO, but not CO, modulates these responses.

Topics: Anaphylaxis; Animals; Bile; Carbon Monoxide; Enzyme Inhibitors; Guinea Pigs; Hemodynamics; Hepatic Veins; Immunization; In Vitro Techniques; Injections; Liver; Liver Circulation; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide; Organ Size; Ovalbumin; Portal Vein; Protoporphyrins; Vascular Resistance; Vasoconstriction; Weight Gain

The antiallergic properties of the 70% ethanol extract from Plumbago zeylanica stems (EPZ) were investigated in the present study. The extract (500, 1000 mg/kg, p.o.) dose-dependently inhibited systemic anaphylactic shock induced by compound 48/80 in mice, reduced homologous passive cutaneous anaphylaxis and skin reactions induced by histamine or serotonin in rats, significant differences were observed at the dose of 1000 mg/kg. In vitro, EPZ (5, 20, 50 microg/ml) concentration-dependently reduced histamine release from rat peritoneal mast cells caused by compound 48/80 and antigen. EPZ (50 microg/ml) markedly increased intracellular cAMP content of rat mast cells. These findings demonstrate that EPZ inhibits mast cell-dependent immediate allergic reactions, which is probably mediated by reducing the release of mediators such as histamine from mast cells via elevating intracellular cAMP level and weakening the inflammatory action of mediators.

Topics: Administration, Oral; Anaphylaxis; Animals; Anti-Allergic Agents; Cyclic AMP; Drugs, Chinese Herbal; Ethanol; Histamine; Histamine Release; In Vitro Techniques; Male; Mast Cells; Mice; Mice, Inbred ICR; Ovalbumin; Passive Cutaneous Anaphylaxis; Peritoneal Cavity; Phytotherapy; Plant Stems; Plumbaginaceae; Rats; Serotonin

It has been proposed that infections with helminths can protect from the development of allergic diseases. However, epidemiological and experimental studies have yielded conflicting results. Therefore we investigated if an infection with Nippostrongylus brasiliensis influenced the development of allergen-induced Th2 cell responses in mice. We found a decrease in allergen-induced airway eosinophilia and Eotaxin levels in the airways when mice were infected with the helminths 8 weeks, and especially 4 weeks, but not 1 or 2 weeks before ovalbumin (OVA)-airway challenge. While OVA-specific IgG1 and IgE serum levels and cutaneous hypersensitivity reactions were not reduced by the helminth infection, there was a reduction in OVA-specific IgG1 and IgE levels in bronchoalveolar lavage fluid of mice. Suppression of allergen-induced airway eosinophilia and reduction of Eotaxin production was not observed in IL-10 deficient mice. In addition, we found that helminth-induced airway eosinophilia and Eotaxin production was strongly increased in IL-10 deficient mice infected with the helminths in comparison to control mice. Taken together, these results show that infection with N. brasiliensis suppresses the development of allergen-induced airway eosinophilia and that this effect may be mediated by IL-10. Our results support the view that helminth infections can contribute to the suppression of allergies in humans.

Topics: Allergens; Anaphylaxis; Animals; Bronchial Provocation Tests; Bronchoalveolar Lavage Fluid; CD4-Positive T-Lymphocytes; Cell Count; Cells, Cultured; Chemokine CCL11; Chemokines, CC; Eosinophils; Helminthiasis, Animal; Immunoglobulin E; Immunoglobulin G; Inflammation; Interferon-gamma; Interleukin-10; Interleukins; Lymph Nodes; Macrophages, Alveolar; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Nippostrongylus; Ovalbumin; Respiratory Hypersensitivity; Respiratory System; Skin Tests; Spleen; Th2 Cells; Vaccination

Upon cross-linking of the high-affinity IgE receptors on mast cells, a family of mitogen-activated protein kinases (MAPKs) is activated. The present study examined the effects of p42/44 MAPK kinase inhibitor U0126 and p38 MAPK inhibitors SB220025 and PD169316 on ovalbumin (OVA)-induced anaphylactic contraction of isolated guinea pig bronchi and release of histamine and peptidoleukotrienes from lung fragments. Guinea pigs were actively sensitized by OVA. OVA induced anaphylactic bronchial contractions, and release of histamine and peptidoleukotrienes from lung fragments. U0126 (0.3-30 microM), but not SB220025 and PD169316 (3-30 microM), slightly suppressed peak OVA-induced bronchial contraction but markedly reduced anaphylactical contraction over a 50-min period in a dose-dependent manner. U0126 did not inhibit bronchial contractions induced by KCl, histamine or leukotriene D4. U0126 produced a slight reduction in OVA-induced release of histamine but a significant inhibition on the release of peptidoleukotrienes from lung fragments. Exogenous arachidonic acid-induced release of peptidoleukotrienes was not blocked by U0126. SB220025 and PD169316 had no effect on OVA-induced release of histamine and peptidoleukotrienes. Our data indicate that inhibitor of p42/44 MAPK kinase, but not p38 MAPK, can reduce antigen-induced release of peptidoleukotrienes leading to a rapid resolution of anaphylactic bronchial contraction, and may have therapeutic potential for allergic asthma.

Topics: Anaphylaxis; Animals; Bronchi; Bronchoconstriction; Butadienes; Calcium-Calmodulin-Dependent Protein Kinases; Enzyme Inhibitors; Guinea Pigs; Histamine; Imidazoles; In Vitro Techniques; Leukotrienes; Male; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Muscle Contraction; Muscle, Smooth; Nitriles; Ovalbumin; p38 Mitogen-Activated Protein Kinases; Pyrimidines; Time Factors

We previously reported that ovalbumin-diphtheria toxin (OVA-DT) fusion protein eliminates mast cells bearing OVA-specific IgE and protects OVA-sensitized mice from fatal anaphylaxis induced by OVA challenge.. To prove the specificity of therapeutic effect of OVA-DT to allergy induced by OVA only and not by other allergens such as human serum albumin (HSA), and to examine the cytotoxic effect of OVA-DT on B cells bearing OVA-specific IgE.. Mice were sensitized with two different antigens, OVA and HSA, and then treated with OVA-DT. The therapeutic effect of OVA-DT on the allergy response to each of allergen was evaluated by anaphylactic test. The effect of OVA-DT on the production of allergen-specific Ig isotypes of the sensitized mice and the cytotoxic effect of OVA-DT on B cells expressing OVA-specific IgE were examined.. OVA-DT suppressed only OVA-induced allergy but not HSA-induced allergy in mice sensitized with a mixture of OVA and HSA. The suppression was prolonged even to the mice boosted with the same allergen 14 days after last treatment of OVA-DT. In addition, when the sensitized mice were boosted with the same allergens 14 days after last treatment of OVA-DT, the mice showed to increase the production of OVA-specific IgG2a/IgG3 and decreased that of OVA-specific IgE. OVA-DT targeted B cells bearing OVA-specific IgE, and killed them by DT-mediated cytotoxicity.. The therapeutic effect of OVA-DT was specific to OVA-induced allergy and the suppression of OVA-induced allergy was continuously shown in the mice boosted with the same allergens. This is considered to be caused by the increase of OVA-specific IgG2a and IgG3, and because of the decrease of OVA-specific IgE by killing of B cells bearing OVA-specific IgE.

Topics: Albumins; Allergens; Anaphylaxis; Animals; B-Lymphocytes; Cytotoxicity, Immunologic; Diphtheria Toxin; Female; Humans; Hypersensitivity, Immediate; Immune Tolerance; Immunoglobulin E; Immunoglobulin G; Immunotherapy; Mice; Mice, Inbred BALB C; Ovalbumin; Serum Albumin

Aerobic training can be defined as any physical exercise that increases the heart rate and enhances the body's intake of oxygen long enough to benefit the condition of the body. Running, cycling, and swimming are examples of aerobic activities. In recent years, the importance of sports in everyday life has been rapidly increasing. Moderate exercise appears to stimulate the immune system. However, healthy elite runners often complain about bronchial symptoms after heavy exercise. Exercise-induced asthma and active systemic anaphylaxis are the most common problems seen in these individuals. The inter-relationship of exercise and the allergy response has not been well studied. This study was designed to examine the effects of regular swim training on body weight, spleen index, the number of lymphocytes, scoring of active systemic anaphylactic shock, proliferative activity of splenic lymphocytes and cytokine levels in BALB/c mice. Thirty mice (6 weeks old) were involved in this study and they were divided into 3 groups: a control group (Control, n = 10), a sensitized group (Sensitized, n = 10), and a sensitized-trained group (Sen-trained, n = 10). The sen-trained group was studied after 10 weeks of regular swim training. All data were expressed as mean and standard deviation by using SPSS (ver.10.0). The swim training caused a decrease in body weight (p < 05), an increase of spleen index, active systemic anaphylaxis, lymphocyte proliferation (stimulated with ovalbumin), and cytokine levels (especially IL-4) when comparing the sen-trained group to the sensitized group (p < .05). These data indicate that there is a link between allergy anaphylaxis and regular swim training. This may be due to increased lymphocyte proliferation (stimulated with ovalbumin), ASAS (active systemic anaphylactic shock) score, and IL-4 cytokine levels after exercise.

Topics: Anaphylaxis; Animals; Body Weight; Interferon-gamma; Interleukin-4; Lymphocyte Count; Lymphocytes; Male; Mice; Mice, Inbred BALB C; Organ Size; Ovalbumin; Spleen; Swimming

An influence was studied in experiment of intragastrically administrated milk cream contaminated with mould fungi spores on systemic anaphylactic reaction gravity in Wistar albino rats sensitized with egg albumin (EA). During 28 days sensitized rats intragastrically received cream containing 10(3) or 10(6) colony forming units of 5 fungal species in one cm3. After being challenged rats developed mild anaphylactic shock followed by elevation of small intestinal permeability for macromolecular tracer polyethylene glycol 4000. An increase of small intestinal permeability was also noticed in unsensitized rats that were fed with cream contaminated with 10(6) spores per cm3. Unexpectedly these effects were not additive: the intestinal permeability in sensitized rats decreased at maximal level of contamination. This may be explained by strengthening of gastrointestinal motility in these animals. Significant elevation of antibody production against EA was revealed in sensitized rats that received cream contaminated by spores at high level. The data obtained signify that milk products fungal contamination that could not be revealed by sense may nevertheless have negative impact on intestinal barrier function and sensitization.

Topics: Anaphylaxis; Animals; Dairy Products; Fungi; Gastrointestinal Motility; Immunoglobulin E; Intestine, Small; Ovalbumin; Polyethylene Glycols; Rats; Spores, Fungal

Enteric neuroimmune interactions in gastrointestinal hypersensitivity responses involve antigen detection by mast cells, mast cell degranulation, release of chemical mediators, and modulatory actions of the mediators on the enteric nervous system (ENS). Electrophysiological methods were used to investigate electrical and synaptic behavior of neurons in the stomach and small intestine during exposure to beta-lactoglobulin in guinea pigs sensitized to cow's milk. Application of beta-lactoglobulin to sensitized preparations depolarized the membrane potential and increased neuronal excitability in small intestinal neurons but not in gastric neurons. Effects on membrane potential and excitability in the small intestine were suppressed by the mast cell stabilizing drug ketotifen, the histamine H(2) receptor antagonist cimetidine, the cyclooxygenase inhibitor piroxicam, and the 5-lipoxygenase inhibitor caffeic acid. Unlike small intestinal ganglion cells, gastric myenteric neurons did not respond to histamine applied exogenously. Antigenic exposure suppressed noradrenergic inhibitory neurotransmission in the small intestinal submucosal plexus. The histamine H(3) receptor antagonist thioperamide and piroxicam, but not caffeic acid, prevented the allergic suppression of noradrenergic inhibitory neurotransmission. Antigenic stimulation of neuronal excitability and suppression of synaptic transmission occurred only in milk-sensitized animals. Results suggest that signaling between mast cells and the ENS underlies intestinal, but not gastric, anaphylactic responses associated with food allergies. Histamine, prostaglandins, and leukotrienes are paracrine signals in the communication pathway from mast cells to the small intestinal ENS.

Topics: Anaphylaxis; Animals; Dinoprostone; Electrophysiology; Fluorescent Antibody Technique; Guinea Pigs; Histamine; Histamine Antagonists; Intestine, Small; Lactoglobulins; Leukotriene C4; Mast Cells; Membrane Potentials; Milk; Neuroimmunomodulation; Neurons; Ovalbumin; Serotonin Antagonists; Stomach; Submucous Plexus; Sympathetic Nervous System; Synaptic Transmission

Anaphylactic shock accidents after allergen exposure are frequent. After immunization with ovalbumin (OVA), a common dietary constituent, we evaluated the efficacy of pretreatment with histamine-receptor or serotonin-receptor blockers administered alone or in combination with a nitric oxide synthase inhibitor (L-NAME) on OVA-induced anaphylactic shock in Brown Norway rats. Animals were allocated to the following groups (n = 6 each): control (0.9% saline); diphenydramine (15 mg kg(-1)); cimetidine (20 mg kg(-1)); diphenydramine + cimetidine; dihydroergotamine (50 microg kg(-1)); diphenydramine + cimetidine + dihydroergotamine; L-NAME (100 mg/kg) alone or associated with diphenydramine, cimetidine, diphenydramine + cimetidine, dihydroergotamine, or diphenydramine + cimetidine + dihydroergotamine. Mean arterial blood pressure (MABP), heart rate (HR), and survival time were monitored for 60 min following treatment. The shock was initiated with i.v. OVA. The MABP drop after i.v. OVA was worsened by diphenydramine and was modestly attenuated by cimetidine, dihydroergotamine, or both together. L-NAME potentiated slightly the effects of cimetidine and dihydroergotamine by lessening the initial MABP decrease, but this transient effect was not sufficient to prevent the final collapse or to improve survival time. Decreased vasodilatory (prostaglandins E2), increased vasoconstrictory (thromboxane B2) prostaglandins, and unchanged leukotriene C4 concentrations were contributory to the overall hemodynamic changes. Thus, the combined blockade of vasodilator mediators (histamine, serotonin, and nitric oxide) slowed the MABP drop in anaphylactic shock, but did not improve survival. More studies are needed to understand these discordant effects.

Topics: Anaphylaxis; Animals; Arteries; Cimetidine; Dihydroergotamine; Dinoprostone; Eicosanoids; Enzyme Inhibitors; Heart; Histamine; Hypotension; Leukotriene C4; Male; Myocardium; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; Ovalbumin; Pressure; Rats; Rats, Inbred BN; Receptors, Serotonin; Serotonin; Thromboxane B2; Time Factors

Anaphylactic shock is an immunoglobulin E (IgE)-dependent hypersensitivity. Biological tests like leucocyte histamine release (LHR) and human basophil activation (HBA), frequently used in human allergy, reflect both the amount of IgE fixed on cells and the cellular reactivity. To assess whether serum-specific IgE from Brown Norway (BN) rats prepared for ovalbumin (OVA)-induced anaphylactic shocks can activate human basophils which has a potential interest in experimental allergy: such a test could rapidly assert an IgE sensitization in laboratory animals genetically T-helper 2 (Th2)-predisposed. Rats (n = 39) were immunized three times (day 0, day 5 and day 21) with OVA injected subcutaneously. One week after the third immunization, a shock was induced with an intravenous (i.v.) bolus of OVA. Sensitization was assessed by passive cutaneous anaphylaxis (PCA) test and dosages of serum IgE antibodies anti-OVA by enzyme-linked immunosorbent assay. Blood basophils were counted before and during the shock. Before the shock induction (at day 21), an LHR test was performed on rat blood, and human basophils were sensitized with rat sera. HBA was demonstrated by the increase in the percentage of cells expressing CD63 antigen membrane, measured by flow cytometry. Twenty-one days after the first subcutaneous (s.c.) immunization, the rat serum induced a significant HBA. HBA was observed neither with the same serum previously heated nor with the serum from nonimmunized rats (NIRs). OVA-specific IgEs were significantly increased in immunized rat (IR) serum. The PCA test was negative when the serum was previously heated (56 degrees C). We never observed any circulating basophils, and LHR test was negative. After OVA i.v. administration, all IRs died rapidly. HBA testing strongly suggests a mediation by specific IgE in the increase of CD63 in BN rats. Thus, HBA test seems useful in assessing whether an experimental allergy was induced in animals genetically predisposed to an immune response, Th2-mediated, like BN rat. We also conclude that rat basophil activation does not participate in the histamine release during anaphylactic shock in sensitized BN rats.

Topics: Anaphylaxis; Animals; Antigens, CD; Basophils; Enzyme-Linked Immunosorbent Assay; Histamine Release; Humans; Immunization; Immunoglobulin E; Ovalbumin; Passive Cutaneous Anaphylaxis; Platelet Membrane Glycoproteins; Rats; Rats, Inbred BN; Tetraspanin 30

Intestinal anaphylaxis triggers neuronal activation in the nucleus tractus solitarius (nTS) of the rat brain stem. Stress may modulate reflex circuitry in the brain stem and facilitate intestinal inflammatory responses. We hypothesized that stress would modulate central neuronal activation during intestinal anaphylaxis. NTS neurons were activated following intestinal antigen challenge in sensitized Hooded Lister rats but not in negative controls (P < 0.05). The number of Fos-positive neurons following intestinal anaphylaxis decreased in animals exposed to water-avoidance stress (P < 0.05), although serum levels of rat mast cell protease II were not different in stressed and unstressed animals, indicating a similar degree of mast cell degranulation. Stress seems to inhibit neuronal activation in the rat brain stem during intestinal inflammation without modulation of the inflammatory response itself. This may have implications for a potential efferent neuronal modulation of inflammatory responses in the gut.

Topics: Anaphylaxis; Animals; Cell Count; Chickens; Intestinal Diseases; Male; Neural Inhibition; Ovalbumin; Proto-Oncogene Proteins c-fos; Rats; Solitary Nucleus; Stress, Physiological

The aetiology of food allergy remains unclear. Although failure to develop or breakdown in oral tolerance has been proposed, the existence of physiologic sensitization routes other than the gastrointestinal tract cannot be excluded.. The purpose of this study is to clarify whether or not exposure to allergen through the skin can promote food allergy.. BALB/c mice were shaved on the back, and a patch impregnated with 100 micro g of ovalbumin (OVA) was applied to the dorsal skin for a 1-week period and then removed. After three courses of sensitization, OVA-specific antibodies in sera were measured, and then mice were orally challenged with 50 mg of OVA. Anaphylactic symptoms, plasma histamine levels, and histology of intestines and lungs after oral challenge were examined.. Epicutaneous (EC) sensitization of mice to OVA induced a high level of OVA-specific IgE. Subsequent oral challenge with OVA resulted in symptoms of systemic anaphylaxis with elevated levels of plasma histamine as well as histological changes in both intestines and lungs. In the presence of anti-IL-4 antibodies, EC sensitization failed to provoke an IgE response, but still induced a Th2-predominant cellular immune response in lungs after oral challenge.. We demonstrated for the first time that food allergy can be induced by allergen exposure through the skin. Our results identify a novel role of EC sensitization in the pathogenesis of food allergy.

Topics: Administration, Cutaneous; Administration, Oral; Allergens; Anaphylaxis; Animals; Female; Food Hypersensitivity; Histamine; Immunoglobulin E; Interleukin-4; Intestines; Lung; Mice; Mice, Inbred BALB C; Ovalbumin; Th2 Cells

The increase in the transcellular passage of intact antigens across the digestive epithelium infected with Helicobacter pylori may interfere with the regulation of mucosal immune responses. The aim of this work was to study the capacity of Helicobacter infection to inhibit the development of oral tolerance or to promote allergic sensitization and the capacity of a gastro-protective agent, rebamipide, to interfere with these processes in mice. Oral tolerance to ovalbumin (OVA) was studied in 48 C3H/He 4-week-old mice divided into four groups: (i) OVA-sensitized mice; (ii) OVA-"tolerized" mice (that is, mice that were rendered immunologically tolerant); (iii) H. felis-infected, OVA-tolerized mice; (iv) and H. felis-infected, OVA-tolerized, rebamipide-treated mice. Oral sensitization to hen egg lysozyme (HEL) was studied in 48 mice divided into four groups: (i) controls; (ii) HEL-sensitized mice; (iii) H. felis-infected, HEL-sensitized mice; and (iv) H. felis-infected, HEL-sensitized, rebamipide-treated mice. Specific anti-OVA or anti-HEL immunoglobulin E (IgE) and IgG1/IgG2a serum titers were measured by enzyme-linked immunosorbent assay. Additionally, the capacity of rebamipide to interfere with antigen presentation and T-cell activation in vitro, as well as absorption of rebamipide across the epithelial monolayer, was tested. H. felis infection led to the inhibition of oral tolerance to OVA, but rebamipide prevented this inhibitive effect of H. felis. H. felis infection did not enhance the sensitization to HEL, but rebamipide inhibited the development of this sensitization. Moreover, rebamipide inhibited in a dose-dependent manner antigen presentation and T-cell activation in vitro and was shown to be able to cross the epithelium at a concentration capable of inducing this inhibitory effect. We conclude that H. felis can inhibit the development of oral tolerance to OVA in mice and that this inhibition is prevented by rebamipide.

Topics: Administration, Oral; Alanine; Anaphylaxis; Animals; Antigen Presentation; Antigens; Chickens; Female; Gastritis; Helicobacter Infections; Immune Tolerance; Immunity, Mucosal; Immunoglobulin E; Immunoglobulin G; In Vitro Techniques; Intestines; Mice; Mice, Inbred C3H; Muramidase; Ovalbumin; Quinolones; T-Lymphocytes

Mast-cell-deficient WBB6F1-W/W(v) mice (W/W(v)) and congenic wild-type (+/+) mice were sensitized by oral administration of 0.1 or 1.0 mg ovalbumin (OVA) in the form of gavage every day for 9 weeks, and active systemic anaphylaxis (ASA) was induced by intraperitoneal injection of OVA. Production of OVA-specific IgG1 in response to oral sensitization of the W/W(v) mice was very high, and the production of IL-4, IL-5 and IL-10 by splenocytes re-stimulated with OVA in vitro was increased. These findings suggest that Th2-dominant helper T-cell activation had occurred. By contrast, production of OVA-specific IgG1 was low in +/+ mice, and no significant increase in production of Th2-type cytokines by the splenocytes of +/+ mice was observed. Population analysis in Peyer's patches by flow cytometry revealed that the proportion of the CD11c(+) cell in the W/W(v) mice was slightly increased after antigen stimulation. Analysis of the cell surface markers of intraepithelial lymphocytes (IELs) by flow cytometry showed that the proportion of TCRgammadelta-T cells was extremely lower in the W/W(v) mice, especially in the antigen sensitized group. The proportion of TCRgammadelta-T cells in the splenocytes of W/W(v) mice was also lower than in +/+ mice. Taken together, the above findings indicate that W/W(v) mice seems to be a good model not only for studying the induction mechanism of food allergy but for examining the role of TCRgammadelta-T cells in food-induced hypersensitivity.

Topics: Anaphylaxis; Animals; Body Temperature; Body Weight; Cytokines; Flow Cytometry; Immunity, Mucosal; Immunization; Immunoglobulin A; Immunoglobulin E; Immunoglobulin G; Intestinal Mucosa; Mice; Mice, Inbred Strains; Ovalbumin; Peyer's Patches; Proto-Oncogene Proteins c-kit; Spleen; T-Lymphocytes; Th1 Cells; Th2 Cells

Food allergy is a common disease without effective treatment. Since strict elimination of food allergens may be difficult, strategies for effective intervention are urgently needed.. The aim was to investigate the prophylactic use of orally administrated FIP-fve, an immunomodulatory protein isolated from the edible mushroom Flammulina velutipes, in a murine model of food allergy.. BALB/c mice were immunized twice intraperitoneally with ovalbumin (OVA), at an interval of 2 weeks. Before and during each period of immunization, FIP-fve (200 microg per mouse) or phosphate-buffered saline was given orally every other day with a total of five doses. Then OVA-specific antibodies and cytokine profiles were determined. Subsequently, the mice were orally challenged with OVA. Symptoms of anaphylaxis, levels of plasma histamine, and histology of intestines were examined.. Mice receiving oral FIP-fve treatment during sensitization to OVA had an impaired OVA-specific IgE response with a Th1-predominant cytokine profile. These mice were protected from systemic anaphylaxis-like symptoms induced by subsequent oral challenge with OVA.. Oral administration of FIP-fve has a Th1-skewing effect on the development of the allergen-specific immune response, and may serve the purpose of immunoprophylaxis for food allergy and other allergic diseases.

Topics: Administration, Oral; Anaphylaxis; Animals; Antigen-Presenting Cells; Cell Division; Female; Food Hypersensitivity; Fungal Proteins; Histamine; Immunoglobulin E; Interferon-gamma; Interleukin-4; Jejunum; Lectins; Lymphocyte Activation; Mice; Mice, Inbred BALB C; Ovalbumin; Th1 Cells

Gastrointestinal allergic disorders represent a diverse spectrum of inflammatory diseases that are occurring with increasing incidence and severity. An essential question concerning these disorders is to determine the specific cells and mediators responsible for specific clinical manifestations. With this in mind, we developed a murine model of oral allergen-induced intestinal inflammation accompanied by strong Th2-associated humoral and cellular responses and focused on the immunopathogenesis of allergic diarrhea. Exposure of OVA/alum-sensitized mice to repeated doses of intragastric OVA induced genetically restricted, dose-dependent, acute diarrhea associated with increased intestinal permeability, eosinophilia, and mastocytosis. Mice developed limited systemic manifestations of anaphylaxis, even though they developed marked intestinal mucosal mast cell degranulation. Notably, experiments involving mast cell depletion (with anti-c-kit mAb), anti-IgE treatment, and Fc epsilon RI-deficient mice indicated a critical effector role for mast cells in mediating allergic diarrhea. Furthermore, allergic diarrhea was dependent upon synergistic signaling induced by serotonin and platelet-activating factor (PAF), but not histamine. These results demonstrate that oral allergen-induced diarrhea associated with experimental Th2 intestinal inflammation is largely mast cell, IgE, serotonin, and PAF dependent.

Topics: Allergens; Anaphylaxis; Animals; Chymases; Diarrhea; Eosinophils; Immunoglobulin E; Intestinal Mucosa; Mast Cells; Mastocytosis; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Ovalbumin; Permeability; Platelet Activating Factor; Serine Endopeptidases; Serotonin; Th2 Cells

Food allergies are generally associated with gastrointestinal upset, but in many patients systemic reactions occur. However, the systemic effects of food allergies are poorly understood in experimental animals, which also offer the opportunity to explore the actions of anti-allergic drugs. The tripeptide D-phenylalanine-D-glutamate-Glycine (feG), which potentially alleviates the symptoms of systemic anaphylactic reactions, was tested to determine if it also reduced systemic inflammatory responses provoked by a gastric allergic reaction.. Optimal inhibition of intestinal anaphylaxis was obtained when 100 microg/kg of feG was given 20 min before the rats were challenged with antigen. The increase in total circulating neutrophils and accumulation of neutrophils in the heart, developing 3 h and 24 h, respectively, after antigen challenge were reduced by both feG and dexamethasone. Both anti-inflammatory agents reduced the increase in vascular permeability induced by antigen in the intestine and the peripheral skin (pinna), albeit with different time courses. Dexamethasone prevented increases in vascular permeability when given 12 h before antigen challenge, whereas feG was effective when given 20 min before ingestion of antigen. The tripeptide prevented the anaphylaxis induced up regulation of specific antibody binding of a cell adhesion molecule related to neutrophil activation, namely CD49d (alpha4 integrin).. Aside from showing that intestinal anaphylaxis produces significant systemic inflammatory responses in non-intestinal tissues, our results indicate that the tripeptide feG is a potent inhibitor of extra-gastrointestinal allergic reactions preventing both acute (30 min) and chronic (3 h or greater) inflammatory responses.

Topics: Anaphylaxis; Animals; Avian Proteins; Bone Marrow Cells; Capillary Permeability; CD18 Antigens; Cell Adhesion Molecules; Chickens; Intestinal Mucosa; Jejunum; Male; Muscle, Smooth; Neutrophil Infiltration; Oligopeptides; Ovalbumin; Rats; Systemic Inflammatory Response Syndrome

1. Mast cells and basophils are believed to trigger allergic reactions and anaphylaxis. They rapidly release histamine (H), a typical mediator of inflammation, in response to antigens. In the mouse, platelets contain much 5-hydroxytryptamine (5HT), an additional inflammatory mediator, while human platelets contain both H and 5HT. Here, we examined the response of platelets in sensitized mice to antigen challenge. 2. Platelets accumulated in the lung and liver almost immediately after intravenous injection of ovalbumin (OVA), in mice sensitized to it, and platelet degranulation occurred during these reactions. 3. These responses of platelets preceded H release from mast cells and/or basophils, occurred at doses of OVA lower than those inducing H release, and contributed to the signs of shock. 4. We reported previously that intravenous injection into mice of LPS (a membrane constituent of gram-negative bacteria) induces a similar platelet response (accumulation of platelets in the lung and liver) and shock. 5. Blood that has passed through the body (other than the digestive tract) passes first to the lungs before being recirculated by the heart, and blood that has passed through the digestive tract passes next to the liver. Thus, our findings suggest that in addition to their role in haemostasis, platelets, tiny anuclear cytoplasts, may be important in both innate and acquired immunity, and that the lung and liver may be the fronts at which platelets wage war on pathogens.

Topics: Anaphylaxis; Animals; Basophils; Blood Platelets; Cell Degranulation; Female; Histamine; Histamine Release; Liver; Lung; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Ovalbumin; Serotonin

Immunotherapy has gradually fallen out of favor for the treatment of many allergic diseases because of the overall convenience, safety, and efficacy of medications. However, investigations suggest that allergen/immunostimulatory sequence oligodeoxynucleotide (ISS-ODN) conjugates (AICs) might have improved safety and efficacy compared with allergen extracts.. We determined whether changes in the ISS-ODN conjugation ratio would effect the immunogenicity and allergenicity of AIC.. Immunogenicity was determined by means of AIC vaccination of mice, followed by analysis of antigen-specific antibody and cytokine responses. The allergenicity of AIC was determined in mast cell release studies and in murine models of anaphylaxis and the Arthus reaction.. AIC induced a stronger immune response than allergen alone or allergen mixed with ISS-ODN, but higher-level ISS-ODN conjugation reduced its immunogenicity modestly. In mast cell degranulation studies AIC was approximately 100-fold less allergenic than native allergen, with stepwise increases in the ODN conjugation ratio leading to stepwise decreases in allergenicity. In anaphylaxis studies death rates were reduced from 100% with native allergen challenge to as low as 0% with high-ratio ISS-ODN AIC challenge. Similar results were obtained in an Arthus reaction model.. These investigations establish that AIC is both significantly more immunogenic and less allergenic than native allergens and the techniques used might have further utility for the standardization and optimization of AIC formulations for use in allergic patients.

Topics: Adjuvants, Immunologic; Allergens; Anaphylaxis; Animal Population Groups; Animals; Arthus Reaction; Binding Sites, Antibody; Cell Degranulation; Cells, Cultured; Epitopes; Female; Immunotherapy; Mast Cells; Mice; Mice, Inbred BALB C; Oligodeoxyribonucleotides; Ovalbumin; Rats; Survival Analysis; Tumor Cells, Cultured

1 Relaxin (RLX) is a multifunctional hormone best known for its role in pregnancy and parturition, that has been also shown to influence coronary perfusion and mast cell activation through the generation of endogenous nitric oxide (NO). In this study we report on the effects of RLX on the biochemical and mechanical changes of ex vivo perfused hearts isolated from ovalbumin-sensitized guinea-pigs induced by challenge with the specific antigen. The possible involvement of NO in the RLX action has been also investigated. 2 A 30-min perfusion with RLX (30 ng ml(-1)) before ovalbumin challenge fully abated the positive chronotropic and inotropic effects evoked by anaphylactic reaction to the antigen. RLX also blunted the short-term coronary constriction following to antigen challenge. Conversely, perfusion with chemically inactivated RLX had no effect. 3 The release of histamine in the perfusate and the accumulation of calcium in heart tissue induced by antigen challenge were significantly decreased by RLX, while the amounts of nitrites in the perfusate were significantly increased, as were NO synthase activity and expression and cGMP levels in heart tissue. 4 These findings indicate that RLX has a protective effect in cardiac anaphylaxis which involves an up-regulation of the NO biosynthetic pathway.

Topics: Anaphylaxis; Animals; Blotting, Western; Calcium; Cell Degranulation; Cyclic GMP; Densitometry; Guinea Pigs; Histamine Release; In Vitro Techniques; Male; Mast Cells; Myocardium; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Ovalbumin; Relaxin; Up-Regulation

Intravenous injection of a lipopolysaccharide (LPS) into mice induces a rapid accumulation of platelets in the lung and liver. When degradation of the accumulated platelets occurs, anaphylactoid shock follows rapidly, the severity of the shock paralleling the quantity of platelets accumulated in the lung. Here we examined the contributions made by LPS structure and the complement system to the platelet response to LPS. BALB/c mice were injected with an LPS from Escherichia coli O8, O9, O111, or K-12, or from recombinant mutants of K-12. The O-regions of the O8 and O9 LPSs consist of a mannose homopolysaccharide (MHP), while that of O111 consists of a heteropolysaccharide (not including mannose), and K-12 LPS lacks an O-region. O111 LPS was devoid of the ability to induce the platelet response or shock, while the ability of K-12 LPS was weak. The 2 recombinant LPSs-each having an O-region (from O8 or O9) linked to K-12 LPS-exhibited activities similar to or stronger than those of their original LPSs. Mannose-binding lectin (MBL) complexed with MBL-associated serine proteases (MASPs) bound strongly to LPSs containing MHP and caused C4 activation. Moreover, the abilities of these LPSs to activate the complement system corresponded well with their abilities to induce the platelet response and rapid shock. These results suggest that the structure of the O-antigen region is important for the platelet response to LPS, and that activation of the lectin pathway of the complement system is involved in this response.

Topics: Anaphylaxis; Animals; Blood Platelets; Complement Activation; Complement C4; Complement C5; Endotoxins; Escherichia coli; Histamine; Humans; Injections, Intravenous; Lectins; Lipopolysaccharides; Liver; Lung; Male; Mannose; Mannose-Binding Lectin; Mannose-Binding Protein-Associated Serine Proteases; Mast Cells; Mice; Mice, Inbred AKR; Mice, Inbred BALB C; Mice, Inbred DBA; O Antigens; Ovalbumin; Pyrilamine; Serine Endopeptidases; Serotonin; Sesquiterpenes; Shock, Septic; Structure-Activity Relationship

Murine models of hypersensitivity to allergens are useful tools for the evaluation of preclinical strategies to down-regulate the IgE response.. To monitor the long-term kinetics of T and B cell responses to allergen as a function of allergen dosage and to investigate the effect of parallel immunization with a second antigen; to correlate B cell response with anaphylaxis.. CBA/J mice were sensitized every other week by subcutaneous injections of phospholipase A2 (PLA2) and/or ovalbumin (OVA) adsorbed to alum. Specific antibody isotype responses, T cell proliferation, T cell cytokine production and anaphylaxis were assessed throughout the sensitization phase.. Low-dose immunization with PLA2 (0.1 microg) favoured a long-term, specific T helper (Th)2 response with high IgE and IL-4 production in contrast to high-dose PLA2 (10 microg) immunization, which biased the immune response towards a Th1 response with high IgG2a and low IL-4 production. Parallel immunization with an unrelated antigen (ovalbumin) had a significant bystander effect on the immunization with PLA2, which was also dose-dependent. Finally, although anaphylaxis as measured by rectal temperature drop was allergen-specific, it could be induced in the high- and low-dose immunization groups, and was not solely dependent on IgE levels.. Though low-dose allergen immunization appears to induce an efficient IgE response, the intensity and quality of this response may be modulated by bystander effects of parallel immunization and does not correlate strictly with anaphylaxis. This observation has relevance to the design of clinical immunotherapy protocols using murine model-based data.

Topics: Allergens; Anaphylaxis; Animals; Antibody Specificity; B-Lymphocytes; Bystander Effect; Cytokines; Disease Models, Animal; Dose-Response Relationship, Immunologic; Female; Follow-Up Studies; Histocompatibility Antigens Class II; Immunization; Immunoglobulin E; Immunoglobulin G; Mice; Mice, Inbred CBA; Ovalbumin; Phospholipases A; Phospholipases A2; T-Lymphocytes

Our previous study using allergen-sensitized murine splenocyte cultures has shown that Lactobacillus casei strain Shirota (LcS), a lactic acid bacterium widely used as a starter for fermented milk products, suppresses IgE production through promoting a dominant Th1-type response mediated by IL-12 induction.. We tried to evaluate the ability of LcS to suppress both IgE response and allergic reactions in vivo using a food allergy model with ovalbumin-specific T cell receptor transgenic (OVA-TCR-Tg) mice.. The ability of heat-killed LcS to induce IL-12 in serum was tested. OVA-TCR-Tg mice were fed a diet containing OVA for 4 weeks and injected with LcS intraperitoneally three times in the first week of this period. Cytokine and antibody secretion by splenocytes, and serum IgE and IgG1 responses were examined. The inhibitory effect of LcS on systemic anaphylaxis induced by intravenous challenge of OVA-fed OVA-TCR-Tg mice with OVA was also tested.. Intraperitoneal injection of LcS induced an IL-12 response in the serum of OVA-TCR-Tg mice. In the food allergy model, LcS administration skewed the pattern of cytokine production by splenocytes toward Th1 dominance, and suppressed IgE and IgG1 secretion by splenocytes. The ability of LcS to modulate cytokine production was blocked by anti-IL-12 antibody treatment. LcS also inhibited serum OVA-specific IgE and IgG1 responses and diminished systemic anaphylaxis.. LcS administration suppresses IgE and IgG1 responses and systemic allergic reactions in a food allergy model, suggesting a possible use of this lactic acid bacterium in preventing food allergy.

Topics: Anaphylaxis; Animals; Antibodies; Cells, Cultured; Cytokines; Food Hypersensitivity; Genes, T-Cell Receptor; Immunoglobulin E; Immunoglobulin G; Interleukin-12; Lacticaseibacillus casei; Male; Mice; Mice, Inbred BALB C; Mice, Transgenic; Ovalbumin; Peptide Fragments; Spleen; Th1 Cells

The influence of stress and diazepam treatment on airway inflammation was investigated in ovalbumin (OVA)-sensitized rats. Animals were injected with OVA plus aluminum hydroxide intraperitoneally (day 0) and boosted with OVA subcutaneously (day 7). From the first to 13th day after sensitization, rats were treated with diazepam, and 1 h later they were placed in a shuttle box where they received 50 mild escapable foot shocks/day preceded by a sound signal (S). Response during the warning (S) canceled shock delivery and terminated the S. On day 14, rats were submitted to a single session of 50 inescapable foot shocks preceded by S and then were challenged with OVA. High levels of stress were detected in shocked animals, manifested as ultrasonic vocalizations. Morphometric analysis of stressed animals revealed a significant increase in both edema and lymphomononucleated cells in airways compared with controls. Diazepam treatment reduced edema in stressed and nonstressed rats. No differences were found in polymorphonucleated cell infiltration. Diazepam treatment reduced lymphomononucleated cell infiltration in stressed animals. These data suggest that stress and diazepam treatment play relevant roles in edema and lymphomononucleated airway inflammation in OVA-sensitized rats.

Topics: Administration, Inhalation; Anaphylaxis; Animals; Anti-Anxiety Agents; Bronchial Diseases; Conditioning, Psychological; Diazepam; Edema; Electroshock; Injections, Intraperitoneal; Lung; Male; Ovalbumin; Pneumonia; Rats; Rats, Wistar; Specific Pathogen-Free Organisms; Stress, Physiological

Activation of nontransmembrane protein tyrosine kinases, such as Lyn and Syk, has been shown to be the earliest detectable signaling response to Fc receptor (Fc epsilon RI) cross-linking on mast cells leading to mast cell degranulation. The present study examined the effects of piceatannol (3,4,3',5'-tetrahydroxy-trans-stilbene, 10-100 microM), a Syk-selective tyrosine kinase inhibitor, on ovalbumin-induced anaphylactic contraction of isolated guinea pig bronchi and release of histamine and peptidoleukotrienes from chopped lung preparations. Pretreatment with piceatannol slightly suppressed ovalbumin-induced peak anaphylactic bronchial contraction but markedly (P<0.05) facilitated relaxation of the anaphylactically contracted bronchi. Piceatannol did not inhibit direct histamine-, leukotriene D(4)- or KCl-induced bronchial contraction, nor revert an existing anaphylactic bronchial contraction. Piceatannol, at 30 microM and above, significantly (P<0.05) prevented ovalbumin-induced release of both histamine and peptidoleukotrienes from lung fragments. Piceatannol did not inhibit exogenous arachidonic acid-induced release of peptidoleukotrienes from lung fragments. Our data show for the first time that inhibition of Syk tyrosine kinase can attenuate anaphylactic bronchial contraction in vitro, probably via inhibition of mast cell degranulation.

Topics: Airway Obstruction; Anaphylaxis; Animals; Bronchoconstriction; Enzyme Inhibitors; Enzyme Precursors; Enzyme-Linked Immunosorbent Assay; Guinea Pigs; Histamine Release; In Vitro Techniques; Injections, Intraperitoneal; Intracellular Signaling Peptides and Proteins; Leukotrienes; Lung; Male; Ovalbumin; Protein-Tyrosine Kinases; Stilbenes; Syk Kinase

Phospholipase A(2) (PLA(2)) is one of the major honey bee venom allergens for humans. To assess the long-term prevention of allergic reactions by DNA vaccination, a PLA(2)-CBA/J mouse model was employed using empty or PLA(2) sequence-carrying DNA plasmids. Early skin application of either DNA construct before (prophylactic approach) or after (therapeutic approach) sensitization with PLA(2)/alum led to reduced PLA(2)-specific IgE and IgG1 titers at 7 mo, with concomitant rise in IgG2a and IgG3. Splenocytes recovered at 5-6 mo after the last DNA administration exhibited a sustained IFN-gamma and IL-10 secretion and reduced IL-4 production. Recall challenge with PLA(2) boosted IFN-gamma and IL-10 secretion, suggesting the reactivation of quiescent memory Th1 lymphocytes. Mice from the prophylactic groups were fully protected against anaphylaxis, whereas 65% of the animals recovered in the therapeutic groups. Th1-polarized immune responses were also active in mice vaccinated with an empty plasmid 32 wk before sensitization with another Ag (OVA). This is the first demonstration that the Ag-coding sequence in DNA vaccine is not necessary to promote immune modulation in naive and sensitized animals for a prolonged period, and has relevance for the understanding of the innate and induced mechanisms underlying gene immunotherapy in long-term treatment of allergy.

Topics: Adjuvants, Immunologic; Anaphylaxis; Animals; Antibody Specificity; Antigens; Bee Venoms; Cells, Cultured; CHO Cells; Cricetinae; Cytokines; Desensitization, Immunologic; Female; Genetic Vectors; Immunoglobulin E; Immunoglobulin G; Immunosuppressive Agents; Lymphocyte Activation; Mice; Mice, Inbred CBA; Ovalbumin; Peptide Fragments; Phospholipases A; T-Lymphocyte Subsets; Th1 Cells; Transfection; Up-Regulation; Vaccines, DNA

The Src family kinase Lyn initiates intracellular signal transduction by associating with a variety of immune receptors such as antigen receptor on B cells and high-affinity Fc receptor (FcR) for immunoglobulin Ig(E) (FcepsilonRI) on mast cells. Involvement of Lyn in the IgE-mediated immediate-type hypersensitivity is well documented, but the physiological significance of Lyn in IgG-dependent, type III low-affinity FcR for IgG (FcgammaRIII)-mediated responses is largely unknown. In this study, we generated a double-mutant mouse strain deficient in both type II FcR for IgG (FcgammaRIIB) and Lyn to exclude any involvement of inhibitory signaling by FcgammaRIIB, which otherwise downregulates FcgammaRIII-mediated cellular responses. FcgammaRIIB-deficient but Lyn-sufficient mice served as controls. The Lyn deficiency attenuated IgG-mediated systemic anaphylaxis in vivo, and significantly reduced calcium mobilization and degranulation responses of bone marrow-derived mast cells (BMMCs) in vitro. However, we found that either interleukin 4 or tumor necrosis factor alpha release by BMMCs was comparable to that from Lyn-deficient and control mice, and the reverse-passive Arthus reaction was equally induced in both mutant mice, indicating that Lyn is not involved in the onset of the IgG-mediated, FcgammaRIII-dependent late phase responses of mast cells. These findings provide us with insight into distinct signaling mechanisms in mast cells underlying the development of diverse pathologies as well as a therapeutic potential for selective treatment of allergic disorders.

Topics: Anaphylaxis; Animals; Antigens, CD; Arthus Reaction; Bone Marrow Cells; Calcium; Cells, Cultured; Cytokines; Disease Models, Animal; Haptens; Immunoglobulin E; Immunoglobulin G; Interleukin-4; Mast Cells; Mice; Mice, Mutant Strains; Ovalbumin; Receptors, IgG; Serotonin; Signal Transduction; src-Family Kinases; Tumor Necrosis Factor-alpha

The role of allergens in asthmatic inflammation is not clearly understood. To elucidate the mechanism of cockroach allergen (CRa)-induced airway disease, we studied three groups of Hartley guinea-pigs sensitized to control, ovalbumin (OA) or CRa. Parameters measured were anaphylactic antibodies by allergy skin test (AST), PCA assay and Western blot, changes in specific airway resistance (SRaw), analysis of bronchoalveolar lavage (BAL) and contracture responses of tracheal muscle (TSM) to non-specific and specific stimuli, in vitro. Both OA and CRa animals showed a similar allergic sensitization (AST and PCA), while Western blot identified several reaginic bands in CRa group compared to a single band in OA group. SRaw illustrated that CRa induce dual-asthmatic responses (4/6) in the CRa group, whereas OA induce only an early asthmatic response (3/6) in the OA group (P<0.01). The average total leukocytes in BALF of the CRa were 27.0x10(6), mostly neutrophils and eosinophils, while those of the OA showed 3.5x10(6), mostly eosinophils, respectively (P<0.0001). TSM responses to non-specific stimuli were similar in both groups (P>0.1), while the antigen-specific TSM contractions were more brisk in the OA group than those of CRa group (P<0.001). Thus, the study indicates that both CRa and OA sensitize guinea-pigs, yet CRa induces more severe and persistent late-phase inflammation than OA. This appears to be related to an influx of neutrophils rather than anaphylactic bronchospasm.

Topics: Airway Obstruction; Allergens; Anaphylaxis; Animals; Asthma; Bronchial Spasm; Bronchoalveolar Lavage Fluid; Cockroaches; Guinea Pigs; Immunization; In Vitro Techniques; Male; Muscle Contraction; Neutrophils; Ovalbumin; Passive Cutaneous Anaphylaxis; Respiratory Muscles; Trachea

For those with allergy, vaccination with a specific allergen has often been used as a major therapeutic measure. However, the universal application of this technique in clinics have been restricted due to its low success rates and the risk of active systemic anaphylactic shock (ASAS). In this regard, we constructed a fusion protein (OVA-DT), ovalbumin (OVA) fused with diphtheria toxin protein (DT), which may exert a specific cytotoxicity to cells bearing OVA-specific IgE. Its therapeutic effect was evaluated in mice (BALB/c) sensitized with OVA (Os-mice). OVA challenges to the OVA-sensitized mice (Os-mice) caused ASAS to death within 30 min, but OVA-DT treatment afforded mice complete protection. When OVA-DT was treated to the Os-mice, none showed the signs of ASAS when re-challenged 48 h after the treatment. OVA-DT itself was not found to be toxic or allergenic in normal mice. The effect of OVA-DT on the biological functions of mast cells was also studied. Binding of OVA-DT to OVA-specific IgE bearing mast cells and the inhibition of histamine release from these cells were observed. In addition, OVA-DT treatment inhibited the proliferation of OVA-specific B cells in mice. In Os-mice treated with OVA-DT, levels of anti-OVA IgG2a in serum and the production of IFN-gamma by splenic lymphocytes were found to increase, but the production of IL-4 by these cells decreased. Re-direction of cytokine profiles from OVA-specific Th2 to OVA-specific Thl is suggested. These results indicate that OVA-DT can protect Os-mice from ASAS due to OVA challenge, because it inactivates OVA-specific IgE-expressing cells, including mast cells and B cells.

Topics: Anaphylaxis; Animals; B-Lymphocytes; Female; Histamine Release; Immunoglobulin E; Interferon-gamma; Interleukin-4; Lymphocyte Activation; Mast Cells; Mice; Mice, Inbred BALB C; Ovalbumin; Recombinant Fusion Proteins

Knowledge of the factors which control IgE production is essential in order to understand the pathogenesis of immediate hypersensitivity reactions. We have studied the extent to which the route and frequency of antigen application as well as different antigen amounts may influence IgE synthesis.. We established sensitisation protocols in BALB/c mice, in which various doses of ovalbumin (Ova) were applied via intranasal, epicutaneous or intraperitoneal routes. Ova-specific antibodies were measured by ELISA. After 6 weeks of sensitisation, anaphylactic shock was measured following intravenous challenge with Ova. In addition, bronchoalveolar lavages were performed in intranasally sensitised mice.. We were able to show that the most efficient IgE production was achieved by long-term antigen application via the airways, leading to local allergic airway pathology. The epicutaneous route of antigen application also induced very high IgE titres, while intraperitoneal sensitisation led to significantly lower IgE levels. After intraperitoneal sensitisation, IgE synthesis was best induced by increasing the frequency of antigen application, but not by increasing the amount of antigen. In all groups of mice, Ova-specific IgE antibodies were high enough to induce systemic allergic symptoms leading to anaphylactic shock. The severity of shock correlated with the amount of specific IgE.. Taken together, our results demonstrate that antigen application via the airways or skin induces IgE synthesis more efficiently than via the intraperitoneal route. Few exposures with high-dose antigen are less efficient than multiple exposures with low doses. Our finding that both the route and the frequency of antigen application strongly influence IgE synthesis may help to understand how environmental antigens lead to allergic sensitisation.

Topics: Administration, Cutaneous; Administration, Intranasal; Allergens; Anaphylaxis; Animals; Antigens; Female; Hypersensitivity, Immediate; Immunoglobulin E; Immunoglobulin G; Injections; Lung; Mice; Mice, Inbred BALB C; Ovalbumin; Peritoneum; Pulmonary Eosinophilia

Disodium cromoglycate (DSCG) has been shown to inhibit the release of mediators from mast cells. In the present study, the effect of DSCG on active anaphylactic reaction was studied in mice. DSCG dose-dependently inhibited the active systemic anaphylactic reaction and serum immunoglobulin (Ig)E production induced by immunization with ovalbumin, Bordetella pertussis toxin and aluminum hydroxide gel. DSCG strongly inhibited IL-4-dependent IgE production by lipopolysaccharide-stimulated murine whole spleen cells. In the case of U266 human IgE-bearing B cells, DSCG also showed an inhibitory effect on the IgE production. These results suggest that DSCG has an anti-anaphylactic activity by inhibition of IgE production from B cells.

Topics: Anaphylaxis; Animals; B-Lymphocytes; Bordetella pertussis; Cell Line; Cromolyn Sodium; Female; Humans; Immunoglobulin E; Lipopolysaccharides; Mice; Mice, Inbred ICR; Ovalbumin; Pertussis Toxin; Spleen; Virulence Factors, Bordetella

gp49B1 is an immunoglobulin (Ig) superfamily member that inhibits FcstraightepsilonRI-induced mast cell activation when the two receptors are coligated with antibodies in vitro. The critical question of in vivo function of gp49B1 is now addressed in gene-disrupted mice. gp49B1-deficient mice exhibited a significantly increased sensitivity to IgE-dependent passive cutaneous anaphylaxis as assessed by greater tissue swelling and mast cell degranulation in situ. Importantly, by the same criteria, the absence of gp49B1 also resulted in a lower threshold for antigen challenge in active cutaneous anaphylaxis, in which the antigen-specific antibody levels were comparable in gp49B1-deficient and sufficient mice. Moreover, the absence of gp49B1 resulted in a significantly greater and faster death rate in active systemic anaphylaxis. These results indicate that gp49B1 innately dampens adaptive immediate hypersensitivity responses by suppressing mast cell activation in vivo. In addition, this study provides a new concept and target for regulation of allergic disease susceptibility and severity.

Topics: Anaphylaxis; Animals; Antigens, Surface; Edema; Female; Male; Mast Cells; Membrane Glycoproteins; Mice; Mice, Inbred BALB C; Mice, Knockout; Ovalbumin; Passive Cutaneous Anaphylaxis; Receptors, Immunologic

We studied the conditions needed to sensitize animals to the oral feeding of food allergens, without induction of tolerance, in order to investigate the allergenicity of orally ingested food proteins. Brown Norway (BN) rats were sensitized by daily OVA (ovalbumin)-gavage or by drinking OVA containing water ad libitum and the ASA (active systemic anaphylaxis) response, as the immediate hypersensitivity response to antigen stimulation after oral sensitization, was examined. The oral administration of OVA by gavage produced a higher OVA-specific IgE response and an increase in serum histamine after antigen challenge, as compared to those produced by drinking water. Next, we examined the effect of murine age, the oral feeding technique and the oral feeding dose on sensitization using BALB/c, B10A and ASK mice. Twenty-week-old mice showed the strongest OVA-specific IgE and IgG1 responses and ASA-associated serum histamine contents increased with gavage in the three different age groups of BALB/c mice. Administering 0.1 mg of OVA by gavage daily for 9 weeks appeared to induce a higher response than administering 1 mg of OVA, in terms of OVA-specific IgE and IgG1 antibody responses and ASA responses. Among the three strains of mice, B10A mice exhibited the highest response in terms of OVA-specific IgE and IgG1 antibody and ASA responses. These findings suggested BN rats and B10A mice were suitable models for oral sensitization with antigen protein and that oral sensitization in mice requires low dose, intermittent antigen intakes.

Topics: Administration, Oral; Age Factors; Allergens; Anaphylaxis; Animals; Disease Models, Animal; Female; Histamine; Hypersensitivity; Immunoglobulin E; Immunoglobulin G; Mice; Mice, Inbred BALB C; Ovalbumin; Rats; Rats, Inbred BN; Species Specificity; Time Factors

IL-4 and IL-13 are key regulators in atopic disorders and both signal through the receptor chain IL-4Ralpha. IL-4 and IL-13 are also the only cytokines known to induce class switching to IgE. We sought to compare allergen-specific IgE responses and allergic reactivity of wild-type (wt) mice with IL-4-/- and IL-4Ralpha-/- mice, which lack both IL-4 and IL-13 functions.. BALB/c wt, IL-4-/- and IL-4Ralpha-/- mice were immunized with ovalbumin intranasally or intraperitoneally and specific antibody titers were measured by ELISA. Bronchoalveolar lavage fluids and lung tissue were analyzed cytologically and histologically. Allergic reactivity was determined by active cutaneous anaphylaxis and anaphylactic shock.. wt mice immunized intranasally or intraperitoneally showed high titers of specific IgE 3 and 6 weeks after primary sensitization, resulting in cutaneous anaphylaxis and anaphylactic shock upon challenge. Intranasal sensitization resulted in airway eosinophilia and goblet cell metaplasia. In contrast, IL-4-/- and IL-4Ralpha-/- mice showed no specific IgE after 3 weeks, but produced high titers after 6 weeks. At this time cutaneous anaphylaxis and anaphylactic shock could be induced as in wt mice, but lung pathology was absent.. We conclude that upon long-term allergen exposure, alternative switch mechanisms independent of IL-4 and IL-4Ralpha may induce IgE but not asthma-like lung pathology. This may be relevant for the development of allergic disease, since long-term allergen exposure is a frequent condition during allergic sensitization.

Topics: Allergens; Anaphylaxis; Animals; Eosinophilia; Female; Immunoglobulin E; Immunoglobulin G; Interleukin-13; Interleukin-4; Metaplasia; Mice; Mice, Inbred BALB C; Mice, Knockout; Ovalbumin; Receptors, Interleukin-4

This study investigates the role of mast cells in the hypotension induced by antigen-mediated anaphylaxis, compound 48/80 and dextran in mast cell-deficient white spotting (Ws/Ws) and normal wild type (+/+) rats. Rats were sensitized with 10 microg of intraperitoneal ovalbumin in saline or saline alone (sham-sensitized). Sensitized rats, both Ws/Ws and +/+ but not sham-sensitized rats, challenged intravenously with ovalbumin exhibited hypotensive responses. There was no evidence of mast cell activation in rat mesentery 20 min after intravenous antigen challenge in sensitized +/+ rats. Hypotension induced by intravenous injection of dextran (Dextran-162, 6%, 2 ml kg(-1)) or compound 48/80 (1 mg kg(-1)) occurred in +/+ rats, but not in Ws/Ws rats, and was inhibited by pretreatment with a combination of chlorpheniramine and cimetidine. Taken together, these data indicate that the hypotensive response induced by antigen-mediated anaphylaxis is independent of mast cell activation, whereas mast cell amines play the main role in the hypotensive response induced by dextran or compound 48/80.

Topics: Anaphylaxis; Animals; Blood Pressure; Cell Degranulation; Chlorpheniramine; Cimetidine; Dextrans; Genotype; Heart Rate; Histamine; Histamine H1 Antagonists; Histamine H2 Antagonists; Hypotension; In Vitro Techniques; Injections, Intraperitoneal; Injections, Intravenous; Male; Mast Cells; Mesentery; Ovalbumin; p-Methoxy-N-methylphenethylamine; Rats; Rats, Wistar; Time Factors

Elevated levels of immunoglobulin (Ig)E are associated with immediate-type allergic reactions. The effect of an aqueous extract of Siegesbeckia glabrescens (Compositae) whole plants (SGWP) on in vivo and in vitro IgE production was studied in mice. SGWP dose-dependently inhibited the active systemic anaphylaxis and serum IgE production induced by immunization with ovalbumin and Bordetella pertussis toxin absorbed to aluminium hydroxide gel. SGWP dose-dependently inhibited IL-4-dependent IgE production by lipopolysaccharide-stimulated murine whole spleen cells. In the case of U266 human IgE-bearing B cells, SGWP also showed an inhibitory effect on IgE production. These results suggest that SGWP has an anti-allergic activity by inhibiting IgE production from B cells.

Topics: Anaphylaxis; Animals; Asteraceae; B-Lymphocytes; Disease Models, Animal; Dose-Response Relationship, Drug; Enzyme-Linked Immunosorbent Assay; Female; Immunoglobulin E; Mice; Mice, Inbred ICR; Ovalbumin; Pertussis Toxin; Phytotherapy; Plant Extracts; Spleen; Virulence Factors, Bordetella

This study evaluates further the anti-inflammatory and anti-allergic properties of polygodial, a sesquiterpene extracted from the barks plant Drymis winteri (Winteraceae). Polygodial (12.8-128.1 micromol/kg, i.p.) 30 min prior, inhibited significantly the mouse paw oedema induced by prostaglandin E2, bradykinin (BK) substance P (SP), dextran, platelet activating factor (PAF) or carrageenan. Polygodial also inhibited arachidonic acid-, capsaicin- and croton oil-induced ear oedema in mice. Polygodial (42.7 micromol/kg, i.p.), significantly inhibited both exudation and cell influx when assessed in the pleurisy induced by SP and histamine, and to a less extent the inflammatory response caused by carrageenan, PAF, BK and des-Arg9-BK. Finally, polygodial (4.2-42.7 micromol/kg, i.p.) produced dose-related inhibition of paw oedema induced by ovalbumin, protecting in a time-dependent manner the anaphylactic shock induced by endovenous administration of ovalbumin in animals which had been actively sensitised by this antigen. These and our previous results indicate that the major component present in the bark of the plant D. winteri, the sesquiterpene polygodial exerts an interesting anti-inflammatory and anti-allergic properties when assessed in rats and mice.

Topics: Anaphylaxis; Animals; Anti-Allergic Agents; Anti-Inflammatory Agents; Carrageenan; Disease Models, Animal; Dose-Response Relationship, Drug; Edema; Female; Hindlimb; Inflammation Mediators; Male; Mice; Ovalbumin; Pleurisy; Rats; Rats, Wistar; Sesquiterpenes

Topics: Anaphylaxis; Animals; Antibodies; Antigens; Dose-Response Relationship, Drug; Gastrointestinal Motility; Male; Oligopeptides; Ovalbumin; Rats; Time Factors

Previously, Regal et al. [Regal, J.F., Fraser, D.G., Toth, C.A., 1993. Role of the complement system in antigen-induced bronchoconstriction and changes in blood pressure in the guinea pig. J. Pharmacol. Exp. Ther. 267, 979-988] demonstrated that preventing complement system activation resulted in inhibition of anaphylaxis in the guinea pig, and that the C-terminal 21 amino acids of guinea pig C3a (C3a-peptide) mimic the symptoms of anaphylactic shock in the guinea pig [Regal, J.F., 1997. Role of the complement system in pulmonary disorders. Immunopharmacology 38, 17-25]. To determine if C3a is an essential mediator of systemic anaphylaxis, the anaphylactic response to ovalbumin (OA) was assessed in guinea pigs genetically deficient in the C3a receptor (C3aR-) compared to their control strain of animals which were C3a receptor positive (C3aR+). In addition, the response to another control strain of animals, Hartley guinea pigs, was determined. Sensitized guinea pigs were anesthetized, and bronchoconstriction and changes in blood pressure were monitored in response to intravenous (i.v.) injection of either C3a-peptide, recombinant human C5a (rHuC5a) or OA. Both Hartley guinea pigs and C3aR+ animals responded similarly to C3a-peptide and rHuC5a. C3aR- animals, however, were unresponsive to C3a-peptide and responded normally to rHuC5a, confirming their functional deficiency of the C3a receptor. In response to OA, C3aR+ animals and Hartley guinea pigs responded with a severe bronchoconstriction, an initial transient hypotension, followed by an increase in blood pressure and a delayed prolonged hypotensive response. In contrast, in C3aR- animals, the increased blood pressure response to OA was significantly prolonged, the delayed hypotensive response was blunted, and the bronchoconstriction was delayed compared to the C3aR+ animals. The difference in the anaphylactic response could not be explained by differing amounts of OA-specific IgG1 antibody or C3a generated during the anaphylactic response. Thus, these data suggest that C3a plays a minor role in the hypotension of systemic anaphylaxis and investigation of a role for other products of complement system activation, either alone or in combination with C3a, is clearly warranted.

Topics: Anaphylaxis; Animals; Blood Pressure; Bronchoconstriction; Complement C3a; Complement C5a; Dose-Response Relationship, Drug; Guinea Pigs; Humans; Immunoglobulin G; Leukocyte Count; Male; Membrane Proteins; Ovalbumin; Peptides; Platelet Count; Receptors, Complement

The mechanism by which orally ingested allergens elicit an IgE response remains unclear because there are few animal models available for investigation of this response.. We tried to develop a murine model suitable for investigation of the IgE response to orally ingested allergens, which would allow us to identify T cells that could promote IgE production.. Ovalbumin (OVA)-specific T-cell receptor transgenic mice were fed a diet containing OVA, and both the serum antibody response and cytokine production by splenocytes were examined.. Oral administration of OVA to transgenic mice led to an increase in the levels of both antigen-specific IgE and total IgE in the sera. Subsequent intravenous challenge of OVA-fed transgenic mice with OVA resulted in anaphylactic shock. Analysis of cytokine production by splenocytes revealed that high IL-4-producing T cells appeared in the spleen 1 week after the start of feeding the OVA diet. T cells from these mice were found to promote IgE secretion by BALB/c B cells in vitro. This helper activity and the levels of IL-4 secretion were diminished after long-term feeding. These findings suggest the possibility that the orally ingested antigen elicited a response by a subpopulation of T cells that produce high levels of T(H2)-type cytokines and that promote IgE secretion, and these same T cells were tolerized by the orally ingested antigen.. This experimental model with transgenic mice may be a useful tool for further studies of the cellular and molecular mechanisms of the T-cell and IgE responses to orally ingested antigens.

Topics: Administration, Oral; Allergens; Anaphylaxis; Animals; Antigens; Cytokines; Epitopes; Female; Immunoglobulin E; Injections, Intraperitoneal; Injections, Intravenous; Mice; Mice, Inbred BALB C; Mice, Transgenic; Models, Immunological; Ovalbumin; Peyer's Patches; Receptors, Antigen, T-Cell; Receptors, Antigen, T-Cell, alpha-beta; Spleen; T-Lymphocytes, Helper-Inducer

Anaphylactic response intensity was quantitatively estimated by means of measuring mean arterial pressure (MAP) and heart rate (HR). Damage to intestinal mucosa was studied by means of morphometry. These indices grew in a dose-dependent way along with the amount of administered egg ovalbumin (OVA). The MAP and HR measurements seem to be useful in a quantitative elucidation of allergic sensitivity in laboratory animals.

Topics: Anaphylaxis; Animals; Antibody Formation; Blood Pressure; Chickens; Disease Models, Animal; Dose-Response Relationship, Drug; Heart Rate; Intestinal Mucosa; Jejunum; Male; Ovalbumin; Rats; Rats, Sprague-Dawley

Despite marked advances in the understanding of allergic responses, the mechanisms regulating gastrointestinal allergy are not very well understood. We have developed a model of antigen-induced eosinophil-associated gastrointestinal allergy and characterized the role of eotaxin and IL-5. Challenge of allergen-sensitized mice with oral allergen, in the form of enteric-coated beads, resulted in marked allergen-specific IgG(1) and IgE, Th(2)-type (IL-4 and IL-5) cytokine production, and eosinophil accumulation in the blood and small intestine. In the genetic absence of eotaxin, a chemokine constitutively expressed in the gastrointestinal tract, eosinophil recruitment into the small intestine was ablated, and these mice developed enhanced eosinophil accumulation in the blood compared with wild-type mice. Interestingly, in the absence of IL-5, allergen challenge promoted partial eosinophil accumulation into the small intestine and a decline in circulating eosinophil levels. Collectively, these results establish that the accumulation of gastrointestinal eosinophils is antigen induced, can occur independent of IL-5, and provides a molecular mechanism to explain the dichotomy between peripheral blood and tissue eosinophilia. Furthermore, eotaxin is identified as a critical regulator of antigen-induced eosinophilic inflammation in the gastrointestinal tract.

Topics: Anaphylaxis; Animals; Chemokine CCL11; Chemokines, CC; Chemotactic Factors, Eosinophil; Cytokines; Eosinophils; Female; Gastrointestinal Diseases; Hypersensitivity; Integrins; Interleukin-5; Male; Mice; Mice, Inbred BALB C; Ovalbumin; Receptors, CCR3; Receptors, Chemokine

Brainstem neurones become activated following intestinal antigen challenge but the signalling mechanisms have not been resolved. Our aim was to determine the extent of brainstem activation after intestinal anaphylaxis induced by chicken egg albumin (EA). An increase in Fos-positive neurones in the nucleus tractus solitarius (nTS) was observed following EA (P<0.05). Fos-expression was decreased following pretreatment with pyrilamine and ondansetron i.p. and to a similar extent when both antagonists were administered together (all P<0.05 vs. control). Indomethacin had no effect on Fos-expression after antigen challenge. 5-HT and histamine but not prostanoids, released following intestinal anaphylaxis, induce nTS activation via histamine H(1)- and 5-HT(3) receptors. Information on the intestinal inflammatory status is relayed centrally and may play a role in reflexes and behavioural responses to activation of the immune system.

Topics: Anaphylaxis; Animals; Brain Stem; Chickens; Histamine H1 Antagonists; Immunohistochemistry; Indomethacin; Intestinal Mucosa; Intestines; Male; Neurons, Afferent; Ovalbumin; Proto-Oncogene Proteins c-fos; Pyrilamine; Rats; Rats, Inbred Strains; Receptors, Histamine H1; Solitary Nucleus

Mast-cell-deficient W/W(v) mice were sensitized by oral administration of 0.1 and 1.0 mg ovalbumin (OVA) by gavage every day for 9 weeks, and active systemic anaphylaxis (ASA) was induced by intraperitoneal injection of OVA. The production of OVA-specific IgE and IgG1 by oral immunization of the W/W(v) mice was high, and the production of IL-4 by splenocytes re-stimulated with OVA in vitro was increased. In contrast, production of OVA-specific IgG2a and IgG2b was low, and production of IFN-gamma by splenocytes after re-stimulation with OVA in vitro was rather decreased. These findings suggest that Th2-dominant helper T-cell activation had occurred. No increase in serum histamine level was observed following ASA induction. However, the plasma platelet-activating factor (PAF) levels of the mice sensitized with 0.1 and 1.0 mg OVA by gavage increased significantly. The increases in plasma PAF correlated well with the ASA-associated decreases in body temperature, suggesting that PAF plays an important role in ASA in W/W(v) mice. Taken together the above findings indicate that W/W(v) mice are a good model not only for studying induction of food allergy but also for examining the role of PAF in food-induced hypersensitivity.

Topics: Administration, Oral; Anaphylaxis; Animals; Body Weight; Disease Models, Animal; Female; Fever; Food Hypersensitivity; Histamine; Injections, Intraperitoneal; Interferon-gamma; Interleukin-4; Mast Cells; Mice; Mice, Mutant Strains; Organ Size; Ovalbumin; Platelet Activating Factor; Th2 Cells

Adjuvants can modulate the levels of anaphylactic- and non-anaphylactic-type IgG1 antibodies produced in response to a particular antigen. Mice immunized with ovalbumin (OVA) in Al(OH)(3) gel (alum) produced mostly the anaphylactic type, irrespective of the s.c. or i.p. route used, and this antibody was not detectable in IL-4(-/-) mice. In contrast, when OVA was injected in complete Freund's adjuvant (CFA), it induced substantial amounts of non-anaphylactic-type IgG1 in both IL-4(+/+) and IL-4(-/-) mice, and some anaphylactic IgG1 antibody in IL-4(+/+) mice only. When IFN-gamma was neutralized by specific mAb in wild-type mice immunized with OVA in CFA, the anaphylactic-type IgG1 antibody increased reaching the same levels as in alum-injected mice. This result indicates that the induction of IFN-gamma by the immunization with CFA down-regulates the production of IL-4-dependent, anaphylactic-type IgG1. Despite their different effects on IgG1 antibody production, both adjuvants dramatically increased the production of IgG2a in IL-4-deprived mice and did not induce any detectable IgE in these mice.

Topics: Adjuvants, Immunologic; Aluminum Hydroxide; Anaphylaxis; Animals; Female; Freund's Adjuvant; Immunoglobulin E; Immunoglobulin G; Interferon-gamma; Interleukin-4; Mice; Mice, Inbred BALB C; Mice, Knockout; Ovalbumin; Passive Cutaneous Anaphylaxis; Rats

The present experiment was undertaken to verify if it is possible to impose Pavlovian conditioning on a lung anaphylactic response (LAR) in rats. Two experiments were done. In the 1st, egg albumin (OVA) aerosol inhalation, which induces signs and symptoms of LAR in OVA- sensitized rats, was paired with an audiovisual cue (conditional stimulus, CS). After reexposure to the CS, the signs and symptoms of LAR were quantitatively measured using a scoring system specially developed for this evaluation; the levels of stress response and anxiety were also quantified. Results showed that the rats reexposed to CS only, displayed LAR scores not significantly different from those reexposed to both CS and the antigen; animals of these groups showed significantly higher LAR scores than rats that received no OVA aerosol challenge. High levels of stress and anxiety were observed 30-40 min after the challenge with OVA aerosol. In the 2nd experiment, rats sensitized with OVA and submitted or not to Pavlovian conditioning were observed in the open-field and in the plus maze apparatus in the absence of OVA aerosol but in the presence of the CS; after behavioral observations the animals were sacrificed for serum corticosterone level determination. Both behavioral and biochemical data showed high levels of stress and anxiety in rats for which the antigen was previously paired with the CS; these changes were not observed in animals which received the antigen 24 h after the presentation of the CS (unpaired) or in those exposed to PBS aerosol (the OVA vehicle) only. The present data show not only that LAR can be submitted to Pavlovian conditioning, but also and importantly, that high levels of stress and anxiety are related to the course of LAR.

Topics: Administration, Inhalation; Aerosols; Anaphylaxis; Animals; Anxiety; Conditioning, Classical; Corticosterone; Exploratory Behavior; Lung Diseases; Male; Ovalbumin; Rats; Rats, Wistar; Stress, Psychological

8-Iso-prostaglandin F2alpha, release from isolated and perfused guinea-pig lung was measured by radioimmunoassay. 8-Iso-prostaglandin F2alpha release was detectable under basal conditions and increased 10-fold during antigen-induced bronchoconstriction, concomitant with the increase of thromboxane B2 and prostaglandin E2. The anti-8-iso-prostaglandin F2alpha serum used in the radioimmunoassay seems to be quite specific for this compound. Pretreatment of lungs with indomethacin (a non-selective inhibitor of cyclooxygenase) reduced 8-iso-prostaglandin F2alpha release under basal conditions and completely abolished the increase observed during lung anaphylaxis. Pretreatment of lungs with NS 398 (N-[2-cyclohexyl]-4-nitrophenyl methanesulphonamide), a selective inhibitor of cyclooxygenase-2, did not change basal or antigen-induced 8-iso-prostaglandin F2alpha release at all. We conclude that under basal conditions guinea-pig lung perfusates contain low levels of 8-iso-prostaglandin F2alpha-like immunoreactivity, which increase 10-fold during antigen-induced bronchoconstriction. This isoprostane seems to be derived from the cyclooxygenation of arachidonic acid via the constitutive form of cyclooxygenase.

Topics: Anaphylaxis; Animals; Bronchoconstriction; Cyclooxygenase Inhibitors; Dinoprost; Dinoprostone; F2-Isoprostanes; Guinea Pigs; In Vitro Techniques; Indomethacin; Lung; Male; Nitrobenzenes; Ovalbumin; Sulfonamides; Thromboxane B2

1. Immunized BP2 mice developed an acute bronchoconstriction in vivo and airway muscle contraction in vitro in response to ovalbumin (OA) and these contractions were dose dependent. 2. Methysergide or atropine inhibited OA-induced bronchoconstriction in vivo and airway muscle contraction in vitro. 3. Neostigmine potentiated the OA-induced bronchoconstriction in vivo and airway muscle contraction in vitro of BP2 mice. This potentiation was markedly reduced by the administration of methysergide or atropine and when the two antagonists were administered together, the responses were completely inhibited. 4. Neostigmine also potentiated the serotonin (5-HT)- and acetylcholine (ACh)-induced bronchoconstriction and this potentiation was significantly reversed by atropine. 5. These results indicate that OA provokes a bronchoconstriction in immunized BP2 mice by stimulating the release of 5-HT, which in turn acts via the cholinergic mediator, ACh.

Topics: Acetylcholine; Anaphylaxis; Animals; Atropine; Bronchoconstriction; Bronchodilator Agents; Cholinesterase Inhibitors; Dose-Response Relationship, Drug; Female; In Vitro Techniques; Methysergide; Mice; Muscle Contraction; Neostigmine; Ovalbumin; Serotonin; Trachea; Vasoconstrictor Agents

Changes in the immunoreactive ET-1 levels during the anaphylactic reaction of airway tissue from ovalbumin-sensitized guinea pigs were investigated. ET-1-immunoreactivity (ET-IR) was detected in the epithelial and smooth muscle layers of tracheal sections from normal guinea pigs and it was enhanced slightly by phosphoramidon (1 microM) treatment. The ET-IR level of the epithelial layer of ovalbumin-treated tissue from actively sensitized animals was slightly higher than that from normal animals, but it was enhanced markedly by phosphoramidon (1 microM) treatment. Furthermore, the mean ET-IR level of homogenates of antigen-treated tracheal tissues from sensitized guinea pigs (22.8 +/- 1.55 fmol mg-1 protein, n = 5) was significantly higher than the corresponding normal level (12.3 +/- 1.21 fmol mg-1 protein, n = 5). These results suggest that increased epithelial airway ET-1 levels contribute to the anaphylactic reaction of guinea pig airways.

Topics: Anaphylaxis; Animals; Antigens; Endothelin-1; Epithelium; Glycopeptides; Guinea Pigs; Immunohistochemistry; Male; Muscle, Smooth; Ovalbumin; Trachea

It is widely accepted that immunoglobulin (Ig)E triggers immediate hypersensitivity responses by activating a cognate high-affinity receptor, FcepsilonRI, leading to mast cell degranulation with release of vasoactive and proinflammatory mediators. This apparent specificity, however, is complicated by the ability of IgE to bind with low affinity to Fc receptors for IgG, FcgammaRII and III. We have addressed the in vivo significance of this interaction by studying IgE-mediated passive systemic anaphylaxis in FcgammaR-deficient mice. Mice deficient in the inhibitory receptor for IgG, FcgammaRIIB, display enhanced IgE-mediated anaphylactic responses, whereas mice deficient in an IgG activation receptor, FcgammaRIII, display a corresponding attenuation of IgE-mediated responses. Thus, in addition to modulating IgG-triggered hypersensitivity responses, FcgammaRII and III on mast cells are potent regulators of IgE-mediated responses and reveal the existence of a regulatory pathway for IgE triggering of effector cells through IgG Fc receptors that could contribute to the etiology of the atopic response.

Topics: Anaphylaxis; Animals; Antigens, CD; Body Temperature; Bone Marrow Cells; Histocytochemistry; Hypersensitivity; Ileum; Immunoglobulin E; Immunoglobulin G; Mast Cells; Mice; Mice, Knockout; Ovalbumin; Receptors, IgG

The smooth muscle of thoracic aorta from guinea pig sensitized with egg albumin (EA) produced an anaphylactic contraction when it was exposed to EA. Experiments were performed to evaluate stress effects on the anaphylactic contraction in guinea pig aortic rings. Two types of stressors were used as immunosuppressor stimuli: physical restraint and shaking of the animals. Both stressors diminished the amplitude of the Schultz-Dale contraction in aortic rings from sensitized guinea pig. The shake stress stimulus interrupted several times during each session induced higher immunosuppression in animals in which the active sensitization and the stress sessions began the same day. Severe restraint stress, prior to active immunization, also suppressed significantly the anaphylactic response. The Schulz-Dale reaction in guinea pig aorta seems to be a valuable technique to study the stress effects on the anaphylactic response.

Topics: Anaphylaxis; Animals; Aorta, Thoracic; Guinea Pigs; Immune Tolerance; Immunization; In Vitro Techniques; Male; Muscle, Smooth, Vascular; Norepinephrine; Ovalbumin; Restraint, Physical; Stress, Mechanical; Vasoconstriction

The effect of lipids administration by gavage (0.4% body weight) given daily during four weeks on the hypersensitivity reaction in trachea, upper and lower bronchi, liver, kidney, mesentery, and pancreas was investigated in male rats. The plasma exudation was assessed by using Evans blue (EB) dye extravasation method. There was a significant difference in the permeability of the organs in nonimmunized rats. The immunization increased the vascular permeability and the response with the organs varied greatly. The effect of lipids on anaphylactic reaction was compared to those of untreated rats (control group). The EB extravasation was significantly increased in the trachea obtained from rats treated with cocoa butter and soybean oil. In the upper bronchi of rats treated with soybean oil, the EB extravasation was increased. However, in the lower bronchi, none of the treatments with lipids changed the extravasation of EB. The same was observed in the liver and kidney. The animals treated with lipids by gavage did not present differences in EB extravasation in the mesentery. However, in the pancreas and duodenum, the treatment with fish and soybean oils and cocoa butter markedly lowered EB extravasation.

Topics: Administration, Oral; Anaphylaxis; Animals; Capillary Permeability; Dietary Fats; Drug Hypersensitivity; Evans Blue; Immunization; Male; Ovalbumin; Rats

Carrot juice was administered orally to BALB/c mice immunized intraperitoneally with dinitrophenylated (DNP)-OVA for about 1 month. The titers of DNP-specific IgE, DNP-specific IgG, and the levels of total IgE in mouse sera were determined. The DNP-specific IgE production by mice fed carrot juice was significantly inhibited. On the other hand, the DNP-specific IgG production and the level of total IgE in mice fed carrot juice were not significantly different from those in control mice. We also examined the effect of feeding carrots on immediate-type hypersensitivity. One hour after antigen stimulation, the ears of mice fed carrots swelled less than those of control mice. Furthermore, the rise in serum histamine in the mice fed carrots under active systemic anaphylaxis was lower than in controls. We then examined the pattern of cytokine production by spleen cells from mice followed by restimulation with DNP-OVA in vitro. The spleen cells from the mice fed carrots produced more interferon-gamma than those from the control group. In contrast, the spleen cells from the mice fed carrots produced less interleukin-4 than those from the control group. Furthermore, the interleukin-12 production of the spleen cells from mice fed carrots was also higher than that of the control group. These findings suggest that feeding carrots improves the helper T cell (Th)1/Th2 balance, inhibiting specific IgE production and antigen-induced anaphylactic response.

Topics: Anaphylaxis; Animals; Anti-Allergic Agents; Cytokines; Daucus carota; Female; Histamine; Immunoglobulin E; Immunoglobulin G; Mice; Mice, Inbred BALB C; Ovalbumin

Immunoglobulin E (IgE) is the principal immunoglobulin involved in immediate hypersensitivities and chronic allergic diseases. The effect of an aqueous extract of Poncirus trifoliata (L) Raf. (Rutaceae) fruits (PTFE) on in vivo and in vitro IgE production was investigated. PTFE dose-dependently inhibited the active systemic anaphylaxis and serum IgE production induced by immunization with ovalbumin, Bordetella pertussis toxin and aluminum hydroxide gel. PTFE strongly inhibited interleukin 4 (IL-4)-dependent IgE production by lipopolysaccharide-stimulated murine whole spleen cells. In the case of U266 human IgE-bearing B cells, PTFE also showed an inhibitory effect on the IgE production. These results suggest that PTFE has an anti-allergic activity by inhibition of IgE production from B cells.

Topics: Aluminum Hydroxide; Anaphylaxis; Animals; B-Lymphocytes; Cells, Cultured; Dose-Response Relationship, Drug; Female; Humans; Immunoglobulin E; Interleukin-4; Lipopolysaccharides; Medicine, East Asian Traditional; Mice; Mice, Inbred ICR; Ovalbumin; Pertussis Toxin; Plant Extracts; Spleen; Virulence Factors, Bordetella

Immediate hypersensitivity reactions in the intestinal mucosa evoke active chloride secretion which enhances the elimination of luminal antigens. The prosecretory actions of histamine and other soluble mediators of anaphylaxis are mediated by submucosal neurons, as are the antisecretory actions of opioid antidiarrheal medications. We tested the hypothesis that the selective delta-opioid receptor agonist [D-Pen2, D-Pen5]enkephalin (DPDPE) alters anaphylaxis-associated ileal anion secretion in vitro. Sheets of ileal mucosa with attached submucosa from guinea pigs sensitized to cow's milk were mounted in Ussing chambers under short-circuit conditions. Mucosal sheets responded to the serosal application of the milk protein, beta-lactoglobulin, with a rapid rise in transepithelial short-circuit current (Isc); in contrast, the egg protein, ovalbumin, was without effect. Pretreatment of tissues with the neuronal conduction blocker, saxitoxin, or the H1 histamine receptor antagonist, diphenhydramine, but not the opioid receptor antagonist, naloxone, significantly reduced mucosal responses to antigen. [D-Pen-2, D-Pen5]enkephalin (0.1 microM, serosal addition) decreased baseline Isc, but potentiated mucosal responses to antigen; its effects were abolished in tissues pretreated with naloxone. These results suggest that immediate hypersensitivity reactions in the guinea pig ileal mucosa are mediated by submucosal neural circuits that are phasically modulated by both mast cell products and opioids.

Topics: Analgesics; Anaphylaxis; Animals; Anti-Allergic Agents; Cricetinae; Diphenhydramine; Drug Interactions; Enkephalin, D-Penicillamine (2,5)-; Ileum; In Vitro Techniques; Lactoglobulins; Male; Milk; Mucous Membrane; Naloxone; Narcotic Antagonists; Ovalbumin; Saxitoxin

Two catechin derivatives (C-1 and C-2) with potent antiallergic activity were isolated from Taiwanese oolong tea by HPLC techniques. From NMR and FAB-MS analyses, the structures of C-1 and C-2 were elucidated as (-)-epigallocatechin 3-O-(3-O-methyl)gallate and (-)-epigallocatechin 3-O-(4-O-methyl)gallate, respectively. The oolong tea leaves contained 0.34% (dry weight) C-1 and 0.20% C-2. Traces of C-2 were detected in only 1 of 15 varieties of green tea tested. C-1 was detected in 13 of 15 green tea varieties; C-1 was most concentrated in tea cultivars classified as Assam hybrids (0. 50-0.82% of dry weight). Quantitative analyses of green tea, oolong tea, and black tea manufactured from same batches of tea leaves showed that neither catechin derivative was produced during the fermentation process. Oral doses of C-1 and C-2 (5-50 mg/kg) significantly inhibited type I allergic (anaphylactic) reactions in mice sensitized with ovalbumin and Freund's incomplete adjuvant. These inhibitory effects exceeded that of the major tea catechin, (-)-epigallocatechin 3-O-gallate, which has known antiallergic properties.

Topics: Anaphylaxis; Animals; Anti-Allergic Agents; Catechin; Magnetic Resonance Spectroscopy; Mice; Ovalbumin; Plant Leaves; Spectrometry, Mass, Fast Atom Bombardment; Taiwan; Tea

The effect of the intratracheal administration of the recombinant SP-C surfactant apoprotein (rSP-C) with phospholipids (PL) in comparison to an ovalbumin induced anaphylactic shock reaction was studied in guinea pigs lungs. Narcotized guinea pigs were challenged by intratracheal administration on test day 24/25 once with a suspension of rSP-C/PL (reconstituted suspension). These animals were priorily sensitized on test day 1, 3 and 5 intraperitoneally with rSP-C/PL suspension or with Ovalbumin (OV) respectively. The following groups were used to assess the anaphylactic lung shock symptoms: group 1: positive control, 1 mg/kg OV protein, 2 ml/kg application volume, (Appl. vol.), N: 5 animals; group 2: 1 mg rSP-C/50 mg PL/0.5 ml/kg Appl. vol., N: 10; group 3: 2 mg rSP-C/100 mg PL/1.0 ml/kg Appl. vol., N: 10; group 4: 4 mg rSP-C/200 mg PL/2.0 ml/kg Appl. vol., N: 10. Clinical signs, mortality, lung weights and histopathological changes were evaluated. Additionally the lungs were investigated immunohistologically with polyclonal antibodies against rSP-C to determine the pulmonary distribution of the intratracheal applied rSP-C. In the OV-treated positive control group, all animals died within 4 minutes after intratracheal challenge, while only 1 animal of group 4 died probably due to an narcosis related respiratory arrest. In the rSP-C/PL treated groups, the lung weights showed a dose-related increase, but nevertheless all these rSP-C-treated groups showed a significant lower lung weight in comparison to the OV treated positive control group. The histopathology assessment of the lungs in the OV-treated animals revealed a severe generalised bronchoconstriction and a hyperemia in connection with a slight interstitial edema in all five animals. The rSP-C/PL-treated animals, which were sacrificed after 3 days, showed no bronchoconstriction but a slight increase in the severity of bronchus-associated infiltration with eosinophilic granulocytes and in the formation of peripheral emphysema, but with no dose-dependency. A slight dose-dependent increase in the deposition of peribronchiolar eosinophilic foreign material was evident. In contrast to this, the number of lipid-laden alveolar macrophages seemed to decrease with increasing doses of rSP-C/PL. The immunohistological investigation with a polyclonal antibody against rSP-C showed an intraalveolar distribution of the intratracheally applied rSP-C which is mainly located in the peribronchiolar alveolar parenchyma.

Topics: Anaphylaxis; Animals; Apoproteins; Disease Models, Animal; Guinea Pigs; Immunohistochemistry; Lung; Male; Ovalbumin; Phospholipids; Pulmonary Edema; Pulmonary Surfactant-Associated Proteins; Pulmonary Surfactants; Recombinant Proteins; Respiratory Distress Syndrome; Trachea

Topics: Amino Acid Sequence; Anaphylaxis; Animals; Bethanechol Compounds; Binding Sites; In Vitro Techniques; Lysine; Male; Molecular Sequence Data; Muscle Contraction; Oligopeptides; Ovalbumin; Rats; Rats, Sprague-Dawley; Tyrosine

We have analyzed in vivo effects of the murine IL-4 mutant Q116D/Y119D (QY), which forms unproductive complexes with IL-4Ralpha and is an antagonist for IL-4 and IL-13 in vitro. Treatment of BALB/c mice with QY during immunization with OVA completely inhibited synthesis of OVA-specific IgE and IgG1. BALB/c-derived knockout mice lacking either IL-4 or IL-4Ralpha also did not develop specific IgE or IgG1, but mounted a much stronger IgG2a and IgG2b response than wild-type mice. In contrast, QY treatment of normal BALB/c mice suppressed specific IgG2a, IgG2b, and IgG3 synthesis, which may indicate the development of tolerance toward the allergen. Associated with the lack of IgE synthesis in QY-treated wild-type mice and in IL-4(-/-) mice used as a control was the failure to develop immediate cutaneous hypersensitivity or anaphylactic shock upon rechallenge. Interestingly, QY treatment also inhibited humoral immune responses and allergic reactivity in SJL/J mice, a strain that did not produce IgE, but displayed IgE-independent mast cell degranulation mediated by specific IgG1. We conclude that QY inhibits Ag-specific humoral immune responses and allergic symptoms mediated either by IgE or IgG1. It needs to be clarified how QY abrogates synthesis of IgG2a, IgG2b, and IgG3, but the induction of tolerance toward nonhazardous protein Ags should be advantageous for therapy of atopic disorders and other Th2-dominated diseases.

Topics: Allergens; Anaphylaxis; Animals; Antibody Formation; Female; Hypersensitivity, Immediate; Immunoglobulin E; Immunoglobulin G; Interleukin-13 Receptor alpha1 Subunit; Interleukin-4; Mice; Mice, Inbred BALB C; Mice, Knockout; Mutation; Ovalbumin; Receptors, Interleukin; Receptors, Interleukin-13; Receptors, Interleukin-4

1. Anaphylaxis-induced contractions of proximal and distal tracheal segments isolated from 14-day ovalbumin (OA)-sensitized rats were studied. 2. OA-induced contractions in distal segments were significantly greater than those observed in proximal segments. 3. Pretreatment of the rats with compound 48/80 or with sodium cromoglycate (SCG) aerosolization significantly reduced OA-induced contractions of trachea distal segments, whereas the contractions of proximal segments were reduced only by compound 48/80. 4. Mepacrine reduced and indomethacin increased the OA-induced contractions in all tracheal segments. Nor-dihydroguaiaretic acid increased the OA-induced contractions in distal tracheal segments, whereas dazoxiben inhibited the contractions in these same segments; neither of these drugs had any effect on the contractions in proximal tracheal segments. 5. The depletion of connective tissue mast cells and subsequent in vitro treatment with indomethacin increased the OA-induced contractions in both segments. 6. We conclude that the contractions of tracheal muscle from OA-sensitized rats depends on the topographic and anatomical origin of the airway tissue. 7. Mediators released by connective tissue mast cells in proximal and distal segments play a pivotal role in this response and may account for variations in the intensity of contraction seen after the addition of OA.

Topics: Anaphylaxis; Animals; Anti-Asthmatic Agents; Cromolyn Sodium; Cyclooxygenase Inhibitors; Indomethacin; Male; Mast Cells; Muscle Contraction; Ovalbumin; Rats; Rats, Wistar; Trachea

Hemorrhage and congestion were not uniformly distributed along the small intestine during systemic anaphylaxis in rats. Duodenum had little hemorrhage and congestion and the terminal ileum had even less. Maximum involvement occurred in jejunum of 13% of rats, in ileum of 47%, and in both jejunum and ileum of 40%. Sequential scoring along the entire length of small intestine revealed different patterns of distribution with more than one peak of intensity in some of the rats. Within a lesioned area, banding was common except where hemorrhage and congestion were so severe as to obliterate all patterns. Banding represented a gradient of injury with respect to the vascular supply. The pale stripes (less severe hemorrhage) contained the penetrating vessels derived from the terminal mesenteric arcades. The dark stripes (more severe hemorrhage) did not contain such vessels. In addition, the mesenteric side of the intestine was less affected than the antimesenteric side. This constituted a second gradient that might also be related to the distance from the vascular supply. In both instances, proximity to larger blood vessels had a protective effect. These two gradients and the variable sites and patterns of distribution have not been described previously in intestinal anaphylaxis. Gradients and the variability of the distribution of lesions in intestinal anaphylaxis should be considered in experiments on pathogenesis and altered function.

Topics: Anaphylaxis; Animals; Caseins; Duodenum; Female; Ileum; Intestine, Small; Jejunum; Male; Ovalbumin; Rats; Rats, Inbred Lew

Homologous passive cutaneous anaphylaxis (PCA) and active cutaneous anaphylaxis (ACA) to ovalbumin and DNP-hapten were studied in the ears of female BALB/c mice by means of assessing Evans blue dye leakage. For the quantitative evaluation of PCA and ACA, a hand-held spectrophotometer and the conventional colorimetric method were used to detect the amount of extravasated dye. The value of deltaE*ab (a numerical expression of color) obtained with the hand-held spectrophotometer and the amount of extravasated dye showed a good correlation. In the mouse ear, the sensitivity of PCA reaction was comparable to that of PCA in the rat, and deltaE*ab in the PCA and ACA reactions correlated well with the dilutions of sera and of the antigen, respectively. Thus, using a hand-held spectrophotometer is a simple, quantitative and sensitive method for ascertaining the extent of immediate-type hypersensitivity in the mouse.

Topics: Anaphylaxis; Animals; Female; Male; Mice; Mice, Inbred BALB C; Ovalbumin; Passive Cutaneous Anaphylaxis; Spectrophotometry

This study investigates the response of small venules to IgE-dependent, antigen-mediated mast cell activation. Intravital microscopy was utilized to visualize 25- to 40-micron mesenteric venules, mast cell degranulation (on-line detection), vascular permeability changes (albumin leakage), leukocyte adhesion, and the formation of platelet aggregates in rats sensitized with 10 microg of intraperitoneal egg albumin (EA) in saline- or sham-sensitized (saline alone) rats. Sensitized rats challenged with EA (1 mg/ml superfusing mesentery), but not sensitized rats challenged with BSA or sham-sensitized rats challenged with EA, exhibited mast cell degranulation with significant time-dependent increases in vascular permeability (inhibited by diphenhydramine, salbutamol, and indomethacin), leukocyte adhesion (inhibited by Web-2086), and the formation of cellular aggregates (platelet), which were associated with intermittent obstruction of venular flow. Anti-platelet antibody, but not anti-neutrophil antibody or fucoidin (selectin antagonist), prevented platelet aggregate formation. Compound 48/80-induced mast cell degranulation caused similar changes in permeability (via different mediators) and leukocyte adhesion but did not induce platelet aggregation. EA-induced platelet aggregation was not inhibited by any of the mediators tested, and platelets isolated from sensitized rats failed to aggregate in response to direct EA challenge, suggesting release of an unidentified inflammatory mediator as the factor initiating platelet aggregation.

Topics: Albuterol; Anaphylaxis; Animals; Azepines; Capillary Permeability; Cell Adhesion; Diphenhydramine; Granulocytes; Immunoglobulin E; Indomethacin; Mast Cells; Methysergide; Microscopy, Video; Ovalbumin; Platelet Aggregation; Platelet Aggregation Inhibitors; Rats; Serum Albumin, Bovine; Splanchnic Circulation; Time Factors; Triazoles; Venules

The roles of mast cells and extrinsic and vagal neural pathways in the anaphylaxis-induced alterations in motility observed at sites remote from antigen exposure were explored. Rats were sensitized to egg albumin (EA) and prepared with 1) electrodes to monitor intestinal myoelectric activity, 2) an isolated intestinal loop, and 3) either intact vagal innervation or a subdiaphragmatic vagotomy. Fasting myoelectric activity was recorded before and after challenge of the jejunum in continuity or the isolated loop with EA or BSA. Intestinal segments and the brain stems were processed for mast cell identification (intestine) or Fos immunoreactivity (brain stem). EA but not BSA challenge of the jejunum or the isolated loop induced altered motility at both sites and diarrhea. Granulated mast cells were significantly reduced at the site local to but not remote from challenge. Vagotomy did not inhibit antigen-induced alterations in motility or diarrhea. The number of Fos-immunoreactive nuclei in vagal sensory or motor nuclei was not significantly altered by vagotomy. Thus antigen challenge of sensitized animals causes mast cell degranulation only at the site of direct challenge but alters motility at sites local and remote from challenge. The remote response requires intact extrinsic but not necessarily vagal neural pathways.

Topics: Anaphylaxis; Animals; Brain Stem; Cell Degranulation; Chickens; Diarrhea; Gastrointestinal Motility; Jejunum; Mast Cells; Motor Neurons; Muscle, Smooth; Neural Pathways; Ovalbumin; Proto-Oncogene Proteins c-fos; Rats; Vagotomy; Vagus Nerve

Ketotifen transdermal delivery systems were prepared using polyisobutylene, liquid paraffin, and fatty acid. In vitro skin penetration studies were conducted in Franz diffusion cells using excised porcine skin to determine the skin permeation rates of ketotifen patches. A trend of increased skin penetration of ketotifen was observed as the amount of liquid paraffin in the patch was increased. In addition, we found that lauric acid was a suitable enhancer for percutaneous absorption of ketotifen. Challenge tests were performed in guinea pigs to determine the therapeutic effect of the delivery systems for the inhibition of anaphylactic shock using varied concentrations of chicken ovum albumin as sensitizer. Our results showed that compared with the treatment of intramuscular administration, the skin patch was more effective and produced higher survival rates. The pharmacokinetics of the ketotifen patch were determined by applying the skin patch to the dorsal skin of rabbits. The plasma levels were maintained constant (42.5-36.4 ng/ml) from 9 to 30 hr. From our study, the prepared ketotifen patch may further be developed for the treatment or prevention of allergic asthma.

Topics: Adhesives; Administration, Cutaneous; Anaphylaxis; Animals; Anti-Allergic Agents; Chromatography, High Pressure Liquid; Female; Guinea Pigs; In Vitro Techniques; Ketotifen; Male; Ovalbumin; Polyenes; Polymers; Rabbits; Skin Absorption; Swine

The effect of systemic and local allergic responses on the mucociliary system of the Eustachian tube was investigated. Egg albumin was administered to guinea pigs via the jugular vein to evoke systemic anaphylaxis in animals previously sensitized with egg albumin. Ciliary activity in the Eustachian tube of sensitized animals was significantly higher than that of control animals. However, the mucociliary clearance time of the Eustachian tube in sensitized animals was significantly longer than in control animals. Local allergic response induced by intratympanic instillation of (BPO)61-BGG induced cilioexcitation and prolonged mucociliary clearance in the guinea pigs sensitized with BPO-BGG. A partial loss of the inner layer of the mucus blanket of the Eustachian tube was observed under electron microscopy. In conclusion, the systemic as well as the local allergic response accelerates ciliary activity but may affect the mucus blanket and induce mucociliary dysfunction in the Eustachian tube, resulting in a predisposition to middle ear diseases.

Topics: Allergens; Anaphylaxis; Animals; Benzeneacetamides; Cilia; Eustachian Tube; Female; gamma-Globulins; Guinea Pigs; Hypersensitivity; Male; Mucociliary Clearance; Ovalbumin; Penicillin G

Virus infections frequently exacerbate asthma, and in some cases may even precipitate its onset. Although this association is well known, experimental investigation has been hampered by the lack of adequate models.. The effects of acute respiratory virus infection on sensitization to aereoallergen were investigated in this study.. Nebulized ovalbumin was used as an aeroantigen in normal mice, and in those infected with respiratory syncytial virus or influenza A.. Both viruses caused transient illness. Ovalbumin inhalation did not induce specific serum antibodies unless the mice were infected at the time of nebulization. In exposed uninfected mice cutaneous challenge with ovalbumin caused no response, but caused acute systemic illness and collapse if previous pulmonary exposure had occurred during respiratory infection. Mice that collapsed in response to cutaneous ovalbumin were found to have IgG1 specific to ovalbumin that was not found in the other mice. Intracellular cytokine staining of splenocyte cultures showed ovalbumin-specific production of IL-4 was enhanced by virus infection during exposure. In CD8+ T cells, ovalbumin-specific interferon-gamma production was also enhanced by co-infection with influenza. Both viruses were equally associated with the induction of anaphylaxis.. These results show that infection with respiratory viruses powerfully augments cellular and humoral immune responses to aeroantigen and provide an experimental model that allows such effects to be investigated.

Topics: Administration, Inhalation; Allergens; Anaphylaxis; Animals; Bronchial Hyperreactivity; Female; Flow Cytometry; Immunoglobulin E; Immunoglobulin G; Influenza A virus; Injections, Intradermal; Mice; Orthomyxoviridae Infections; Ovalbumin; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Respiratory Tract Infections; Spleen; Weight Loss

1. We examined the effect of TYB-2285 on the acute phase and the late phase of lung anaphylaxis in rats. 2. TYB-2285 (3-30 mg/kg PO) inhibited antigen-induced bronchoconstriction and TxB2 production during the acute phase of lung anaphylaxis in a dose-dependent manner. 3. Ketotifen fumarate (30 mg/kg p.o.) inhibited bronchoconstriction and TxB2 production less potently than TYB-2285. 4. TYB-2285 (30 mg/kg p.o.) inhibited the accumulation of neutrophils during the late phase of lung anaphylaxis significantly without a significant change in total cells. 5. Hydrocortisone acetate (100 mg/kg p.o.) inhibited the accumulation of total cells as potent as neutrophils.

Topics: Anaphylaxis; Animals; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Antigens; Bronchoconstriction; Hydrocortisone; Ketotifen; Lung; Male; Neutrophils; Nitriles; Ovalbumin; Rats; Thromboxane B2

We have investigated the antigen-stimulated release of calcitonin gene-related peptide (CGRP) from ovalbumin-sensitized guinea-pig isolated hearts and the interaction with other mediators of anaphylaxis released concomitantly. It was found that antigen challenge caused a significant increase of CGRP release (from basal 31.2 +/- 2.9 to 51.6 +/- 4.9 fmol/5 min). Anaphylactic CGRP release was significantly attenuated in the presence of the cyclooxygenase inhibitor indomethacin while the 5-lipoxygenase inhibitor Bay-X1005 ((R)-2-[4-quinolin-2-yl-methoxy)phenyl]-2-cyclopentyl acetic acid) had no significant effect. Combined treatment with the histamine receptor (H1,H2) antagonists mepyramine and cimetidine also significantly attenuated anaphylactic release of CGRP. Under control conditions antigen injection increased release of cysteinyl-leukotrienes (LT), thromboxane (TXB2) and 6-keto-prostaglandin (PG)F1 alpha from basal values of 0.96 +/- 0.09, 2.7 +/- 0.7 and 3.4 +/- 0.28 ng/5 min respectively, to 5.9 +/- 0.9, 48.4 +/- 3.4 and 6.9 +/- 1.4 ng/5 min. Indomethacin abolished the release of cyclooxygenase products of arachidonate metabolism and simultaneously increased cysteinyl-LT release significantly (8.8 +/- 1.4 ng/5 min). Conversely Bay-X1005 completely abolished cysteinyl-LT release and had no significant effect on anaphylactic release of TXB2 and 6-keto-PGF1 alpha. Simultaneous blockade of H1 and H2 receptors abolished release of 6-keto-PGF1 alpha, while release of TXB2 and cysteinyl-LT was not significantly affected. The results indicate that CGRP is not a primary mediator of the immediate hypersensitivity reaction of the heart, but is in turn released by arachidonic acid metabolites of the cyclooxygenase pathway and histamine. In contrast, LT obviously do not contribute to anaphylactic CGRP release. CGRP is a potent coronary vasodilator and could act as endogenous functional antagonist of vasoconstrictor mediators also released during cardiac anaphylaxis such as cysteinyl-LT, platelet activating factor and TXA2.

Topics: 6-Ketoprostaglandin F1 alpha; Anaphylaxis; Animals; Calcitonin Gene-Related Peptide; Cimetidine; Coronary Circulation; Cyclooxygenase Inhibitors; Guinea Pigs; Heart; Histamine H1 Antagonists; Histamine H2 Antagonists; In Vitro Techniques; Indomethacin; Leukotriene C4; Lipoxygenase Inhibitors; Myocardium; Ovalbumin; Pyrilamine; Quinolines; Thromboxane B2

We attempted to elicit active anaphylaxis to ovalbumin, or passive IgE- or IgG1-dependent anaphylaxis, in mice lacking either the Fc epsilonRI alpha chain or the FcR gamma chain common to Fc epsilonRI and Fc gammaRI/III, or in mice lacking mast cells (KitW/ KitW-v mice), and compared the responses to those in the corresponding wild-type mice. We found that the FcR gamma chain is required for the death, as well as for most of the pathophysiological changes, associated with active anaphylaxis or IgE- or IgG1-dependent passive anaphylaxis. Moreover, some of the physiological changes associated with either active, or IgG1-dependent passive, anaphylactic responses were significantly greater in Fc epsilonRI alpha chain -/- mice than in the corresponding normal mice. Finally, while both KitW/KitW-v and congenic +/+ mice exhibited fatal active anaphylaxis, mast cell-deficient mice exhibited weaker physiological responses than the corresponding wild-type mice in both active and IgG1-dependent passive systemic anaphylaxis. Our findings strongly suggest that while IgE antibodies and Fc epsilonRI may influence the intensity and/or kinetics of some of the pathophysiological changes associated with active anaphylaxis in the mouse, the mortality associated with this response can be mediated largely by IgG1 antibodies and Fc gammaRIII.

Topics: Anaphylaxis; Animals; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal; Cell Degranulation; Female; Heart Arrest; Heart Rate; Immunization; Immunoglobulin E; Immunoglobulin G; Male; Mast Cells; Mice; Mice, Inbred BALB C; Mice, Mutant Strains; Mortality; Ovalbumin; Receptors, IgE; Receptors, IgG

Mites are the most common aeroallergen in human allergic asthma. However, no animal model of mite-induced allergic airway inflammation has been reported before. In this study, an animal model of mite-induced allergic airway inflammation in guinea pigs was developed.. Firstly, we found that two intraperitoneal injections of 100 micrograms crude mite extract (CME), but not multiple aerosol inhalations of 10 mg/ml CME, can cause sensitization in guinea pigs. The sensitization to mites was confirmed by the measurement of serum antimite antibody titer and the detection of anaphylactic bronchoconstriction after intravenous injection of CME solution. Then, single or multiple aerosol challenges with different concentrations (8, 4 or 1 mg/ml) of CME in these sensitized animals were performed. The total white cell and differential counts in the bronchoalveolar lavage (BAL) fluids were studied at different time intervals after challenge in different animals, and tracheal pathology was performed to detect the allergic airway inflammation. For comparison with the study in animals treated with CME, a BAL study in animals treated with ovalbumin was also performed.. The inhalation challenge of CME aerosol in sensitized animals caused prolonged eosinophilia in BAL fluid which persisted for at least 7 days after single challenge. Neither inhalation challenge at higher concentrations of CME aerosol nor repeated inhalation challenges increased the degree of eosinophilia in BAL fluid compared to a single challenge. Using the same procedures, we also found that the mite model caused more eosinophilia in BAL fluid than did ovalbumin.. This is the first report of an animal model of mite-induced allergic airway inflammation in guinea pigs which can provide us with a useful model to study airway inflammation of mite-induced asthma in humans.

Topics: Allergens; Anaphylaxis; Animals; Antibodies, Anti-Idiotypic; Asthma; Bronchial Provocation Tests; Bronchoalveolar Lavage Fluid; Bronchoconstriction; Guinea Pigs; Humans; Leukocyte Count; Male; Mites; Ovalbumin; Respiratory Hypersensitivity

Topics: Acrylates; Anaphylaxis; Animals; Benzoates; Enzyme Inhibitors; Guinea Pigs; Heart; Histamine Release; Kinetics; Male; Ovalbumin; Phospholipases A; Phospholipases A2; Thromboxane B2

Although it is commonly accepted that the immune response is affected by malnutrition there are very few data about its effect in allergic diseases.. The aim of the present study was to investigate the effect of malnutrition in allergic lung inflammation.. An anaphylactic reaction was induced in rat lungs and the increased vascular permeability was measured in the trachea, internal and external bronchi and parenchyma by the Evans blue extravasation method. These studies were conducted in two dietary groups: one fed a normoproteic diet (18%) and the other a hypoproteic diet (4.5%). When the animals were 60 days old the group fed the hypoproteic diet presented a reduction of 77.86% in bodyweight, 63.3% in food intake and 36% in plasma protein concentration characterizing a severe protein-calorie malnutrition.. The anaphylactic reaction in the lungs induced a significant increase in vascular permeability in the trachea and bronchi of both dietary groups. However, the intensity of this effect was significantly lower in the malnourished group. Analysis of immunoglobulin isotypes in the serum by ELISA showed that whereas IgG1 and IgG2a levels were similar in both groups, the levels of IgE were significantly lower in the malnourished animals. Moreover, the levels of antigen-specific IgG1, IgG2a and IgE were all significantly inhibited by the protein-calorie malnutrition. When antibodies were passively transfered to the malnourished rats, they developed a reaction as intense as the normoproteic group.. These results suggest that the capacity to release inflammatory mediators and the vascular response to these mediators is not affected by this type of malnutrition and, therefore, the diminished response of the airways reported here is probably due to the lower levels of anaphylactic antibodies produced by the malnourished rats.

Topics: Anaphylaxis; Animal Nutritional Physiological Phenomena; Animals; Blood Proteins; Body Weight; Capillary Permeability; Diet, Protein-Restricted; Female; Immunization, Passive; Immunoglobulin E; Immunoglobulin G; Lung; Male; Nutrition Disorders; Ovalbumin; Rats; Rats, Wistar; Respiratory Hypersensitivity

The anti-anaphylactic action of potassium channel openers was studied and reported in this paper. Minoxidil(Min) was shown to inhibit passive cutaneous anaphylaxis in rats. Diazoxide (Dia) and Min were found to inhibit antigen-induced guinea-pig ileum smooth muscle contraction in vitro. Min was shown to antagonize 5-HT-induced capillary permeability in rat skin. Dia was demonstrated to inhibit histamine release from rat peritoneal mast cells induced by A23187 and compound 48/80, but it failed to antagonize guinea-pig ileum smooth muscle contraction induced by histamine in vitro. These results provide evidence that potassium channel openers may be a new group of inhibitors of histamine release and indicate that the mechanism of its anti-anaphylactic action may be related to its potassium channel opening effect. As a result of this effect, Ca2+ influx to the mast cells decreases and Ca2+ release from calcium storage was inhibited, thus inhibiting histamine release.

Topics: Anaphylaxis; Animals; Capillary Permeability; Diazoxide; Female; Guinea Pigs; Histamine; In Vitro Techniques; Ion Channel Gating; Male; Mast Cells; Minoxidil; Muscle Contraction; Ovalbumin; Passive Cutaneous Anaphylaxis; Potassium Channels; Random Allocation; Rats; Rats, Sprague-Dawley

It has been suggested that kinins may play a role in allergic pathophysiology of the airways, contributing to bronchoconstriction and oedema formation. Raised levels of kinin generating enzymes and kinins are found in the airways during allergic responses.. Using an in vivo animal model of allergen induced increase in airways resistance we investigated the effects of the bradykinin antagonist Hoe 140, in order to assess the possible contribution of kinins to this response.. Guinea-pigs were sensitized and challenged with ovalbumin (OA) or saline via the endotracheal route and the resulting increase in airways resistance was measured by whole body plethysmography. At 240 min after challenge, bronchoalveolar lavage fluid (BALF) was taken and albumin content and kallikrein-like activity determined by rocket immunoelectrophoresis and use of artificial substrates respectively. Pretreatment of animals with the bradykinin antagonist Hoe 140 at 6.7, 20 or 66.7 nmol/kg or aprotinin (46,000 kallikrein inhibitor units/kg) was by i.p. injection 10 min before challenge.. Pre-treatment with Hoe 140 dose dependently attenuated the increase in airways resistance following allergen challenge. Kallikrein-like activity and albumin in BALF were unaltered. Aprotinin reduced the kallikrein-like activity in BALF but did not alter airways resistance.. Kinins may contribute to a significant part of allergen-induced airways resistance increase in this model but not via an effect on plasma extravasation.

Topics: Airway Resistance; Albumins; Anaphylaxis; Animals; Aprotinin; Bradykinin; Bronchoalveolar Lavage Fluid; Dose-Response Relationship, Drug; Guinea Pigs; Lung; Male; Ovalbumin; Permeability

The ability of the Chelidonium majus L. alkaloid derivative Ukrain (UK) to inhibit ovalbumin-induced sensitization was tested in BALB/c and F1(BALB/c x C57BL/6J) mice. UK introduced into the mice in the mixture with antigen (ovalbumin) and adjuvant (alum) inhibited the sensitization of mice, reflected in lower anti-OA IgE antibody response and decreased antigen-induced histamine release from mast cells isolated from peritoneal cavities of sensitized mice. The effect of UK on the antigenicity of ovalbumin (OA) in anaphylaxis was tested in heterologous passive cutaneous anaphylactic (PCA) reaction on rats. The results show that the OA prepared in the mixture with UK had a decreased ability to react with anti-OA IgE antibodies raised against native OA in mice and fixed on the surface of rat mast cells in heterologous PCA reactions. The results suggest that UK pretreatment of OA may affect its antigenic property and the ability to react with anti-OA IgE antibodies raised against the native IgE molecules.

Topics: Alkaloids; Anaphylaxis; Animals; Antibodies, Anti-Idiotypic; Antineoplastic Agents; Berberine Alkaloids; Dose-Response Relationship, Drug; Female; Immunization; Immunoglobulin E; Mast Cells; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Ovalbumin; Phenanthridines; Rats; Rats, Wistar

In this study we show that the pathophysiology of anaphylaxis includes generation of nitric oxide (NO), a very powerful, short-acting vasodilator. Guinea-pigs sensitized to ovalbumin were treated with 200 microgram/kg diphenylene iodonium (DPI), and NO synthase inhibitor, prior to antigen challenge. Mortality following the challenge fell from 71 to 39% (p < 0.001, n = 59). In the Langendorff preparation perfused isolated hearts from sensitized guinea-pigs were challenged to initiate cardiac anaphylaxis. The coronary flow rate (CFR), a direct reflection of coronary arterial resistance, was reduced by antigen challenge to 56 +/- 4% (n = 16) of the basal rate. DPI (2 micrograms/ml) intensified the antigen-induced fall in CFR to 13 +/- 3% of control (p < 0.005, n = 5), and the false substrate for NO, L-N-methylarginine, to 37 +/- 3% (p < 0.05, n = 4). Sodium nitroprusside (SNP), a NO generator, raised the basal CFR by 46% (from 11.2 +/- 1.7 ml/min to 16.3 +/- 1.9 ml/min) and blunted the antigen-induced fall in CFR. Paradoxically, DPI, which can inhibit flavoprotein enzymes other than NO synthase, potentiated the vasodilator effect of SNP, raising the basal CFR by 116%. Together these results strongly indicate that the vasodilator NO is generated in anaphylaxis. However, whereas in the heart it may function as a counterweight to the vasospasm of the coronary arteries, in the intact animal it appears to be a major contributor to the potentially lethal hypotension of anaphylactic shock.

Topics: Anaphylaxis; Animals; Coronary Circulation; Guinea Pigs; Male; Nitric Oxide; Nitric Oxide Synthase; Nitroprusside; omega-N-Methylarginine; Onium Compounds; Ovalbumin; Regional Blood Flow; Serine Proteinase Inhibitors; Sulfhydryl Reagents; Vascular Resistance

The release of histamine, eicosanoids and catecholamines were measured after induction of anaphylaxis in isolated guinea-pig hearts. The concentration-time profile of these mediators was compared with changes of cardiac parameters. The histamine and catecholamine levels of the coronary effluent were determined at 10 s intervals; thromboxane and prostacyclin levels at 60 s intervals. The release of histamine and norepinephrine were maximum between 20 and 30 s after the antigen challenge and decreased rapidly within 60 s. Thromboxane and prostacyclin increased to a maximum after 3 min and declined slowly within 10 min. The rise in histamine release was correlated with tachycardia. The release of thromboxane was correlated with the increase of coronary perfusion pressure. Cimetidine inhibited the tachycardia and clemastine reduced bradyarrhythmia. The inhibition of lipoxygenase and cyclooxygenase also reduced the rise in the perfusion pressure. These data suggest that different mediators are time-dependently involved in anaphylaxis-induced cardiac changes.

Topics: 6-Ketoprostaglandin F1 alpha; Anaphylaxis; Animals; Catecholamines; Eicosanoids; Epinephrine; Guinea Pigs; Heart; Histamine Release; Kinetics; Leukotrienes; Male; Norepinephrine; Ovalbumin; Platelet Activating Factor; Thromboxane B2

Following sensitization to ovalbumin (OA), male Wistar rats were pretreated with naloxone (20 mg/kg i.p.) and subjected to antigen challenge (3 mg OA i.p.). Naloxone exacerbated both systemic and intestinal anaphylaxis when injected 10 and 90 min before the antigen challenge. This was evidenced by a more pronounced drop in rectal temperature, higher hematocrit values, and by an enhanced elevation of basal short-circuit current (an indication of the secretory tone of the small intestine studied in Ussing chambers). Pretreatment with an equipotent does of methylnaloxone (200 mg/kg i.p.), a peripherally acting opiate antagonist, exacerbated the indices of intestinal anaphylaxis but had no apparent effect on indices of systemic anaphylaxis. Thus, our data strongly suggest that in the rat, components of the systemic hypersensitivity reaction are mediated through central opioid receptors, whereas the changes in gut function characterizing intestinal anaphylaxis are mediated through peripheral opioid receptors.

Topics: Anaphylaxis; Animals; Biological Transport; Cell Membrane Permeability; Chlorides; Hematocrit; Histamine Release; Hypothermia; Immunization; Intestinal Absorption; Male; Naloxone; Neuroimmunomodulation; Ovalbumin; Oxymorphone; Rats; Rats, Wistar; Receptors, Opioid; Specific Pathogen-Free Organisms; Water

1. In sensitized guinea-pigs, the effects of gamma-aminobutyric acid (GABA) and GABAmimetic drugs have been investigated on tracheal segments contracted by cumulative application of an allergen (ovoalbumin, OA) and on serosal mast cells. The same drugs have also been tested on activation of alveolar macrophages isolated from unsensitized guinea-pigs. 2. Superfusion with GABA (1-1000 microM) reduced the contraction intensity of tracheal strips. The effect of GABA (100 microM) was not affected by the carrier blockers, nipecotic acid and beta-alanine (300 microM each). It was mimicked by the GABAB agonist (-)-baclofen (100 microM) but not 3-aminopropanephosphinic acid (100 microM, 3-APA). The GABAA agonist, isoguvacine (100 microM) did not exert any effect. GABA (10 microM)-induced inhibition of tracheal contractions was reduced by the GABAB antagonist, 2-hydroxysaclofen (100 microM, 2-HS), but not by the GABAA antagonist, bicuculline (30 microM). 3. The reduction in contraction intensity induced by GABA (100 microM) was prevented by a 40 min preincubation of tracheal strips with capsaicin (10 microM), but not tetrodotoxin (TTX, 0.3 microM). The effect of GABA (1000 microM) was absent after preincubation with indomethacin (2.8 microM) but unmodified when nordihydroguaiaretic acid (NDGA, 3.3 microM) was used. Finally, removal of the epithelium prevented the GABA effect. 4. Anaphylactic histamine release from serosal mast cells isolated from sensitized animals was not affected either by GABA (10-1000 microM) or the selective receptor agonists (-)-baclofen (0.1-1000 microM) and isoguvacine (10-1000 microM). The release of platelet-activating factor (PAF) from alveolar macrophages stimulated by formyl-Met-Leu-Phe (FMLP; 1 microM) was modified neither by GABA (100 microM)nor by (-)-baclofen (100microM).5. In conclusion, these data show that GABA can inhibit allergic phenomena in the guinea-pig airways through activation of GABAB receptors. An involvement of neuropeptidergic sensory structures is suggested but a role for epithelial cells and arachidonate metabolites is not definitely proved.

Topics: Anaphylaxis; Animals; beta-Alanine; Bronchial Hyperreactivity; Capsaicin; Drug Interactions; Epithelial Cells; GABA Agonists; GABA Antagonists; gamma-Aminobutyric Acid; Guinea Pigs; Histamine Release; Macrophage Activation; Macrophages, Alveolar; Male; Mast Cells; Muscle Contraction; Muscle, Smooth; N-Formylmethionine Leucyl-Phenylalanine; Nipecotic Acids; Ovalbumin; Platelet Activating Factor; Proline; Receptors, GABA; Tetrodotoxin; Trachea

The involvement of the sympathetic and dopaminergic systems on blood neutrophilic leucocytosis observed during anaphylaxis was investigated. Blood neutrophil counts impressively increased 1 h after intravenous injection of ovalbumin (OVA, 250 micrograms/kg) into OVA-immunized rats. The increase in neutrophil counts induced by OVA was abrogated after catecholamine depletion by reserpine. Either adrenalectomy or the alpha- and beta-adrenoceptor antagonists phentolamine and propranolol, respectively, had only minor inhibitory effects on neutrophilia induced by antigen. On the other hand, pretreatment with the dopaminergic antagonists chlorpromazine and pimozide significantly inhibited the neutrophilia. The intravenous injection of apomorphine, a dopaminergic agonist, increased neutrophil counts in naive animals, while chlorpromazine completely inhibited this phenomenon. These results suggest that dopaminergic mechanisms play a role in the systemic neutrophilia observed during anaphylactic shock.

Topics: Adrenergic Antagonists; Anaphylaxis; Animals; Dopamine Antagonists; Leukocytosis; Male; Neutrophils; Ovalbumin; Rats; Rats, Wistar; Reserpine

The purpose of this study was to assess the activity of some marketed products in ocular non-immune and immune type I hypersensitivity reactions, and during intra-ocular type III hypersensitivity. In order to compare these activities, we improved and validated three different models of ocular allergic reaction already known for their ability to reproduce allergic conjunctivitis or uveitis. Allergic conjunctivitis was induced by ocular immediate hypersensitivity after instillation of compound 48/80 in the rat, or an active anaphylaxis reaction with ovalbumin immunisation and challenge in the guinea pig. Uveitis was induced by a reverse passive anaphylaxis reaction using intra-vitreal rabbit anti-bovine IgG anti-serum sensitisation and intravenous bovine gamma-globulin challenge in the rabbit. Clinical scores and blood-tissue permeability indices were studied. Using the same schedule of ocular instillation, the effects of Livostin (levocabastine 0.05%), Almide (lodoxamide 0.1%), Opticrom (sodium cromoglycate 2%), Ocufen (flurbiprofen 0.03%), Acular (ketorolac 0.5%) and 0.3% chlorpheniramine maleate were compared to positive and negative controls. We demonstrated the potent activity of chlorpheniramine maleate 0.3% and Livostin in both allergic conjunctivitis models. Significant activity was also evidenced with Almide, which was only active in the non-immune allergy model, while Opticrom was definitely not active in these models. In the uveitis model, Acular and Ocufen are active and potent drugs, while Livostin and Almide were not active. These results are discussed with respect to the models used and the mediators involved.

Topics: Anaphylaxis; Animals; Blood Proteins; Capillary Permeability; Conjunctivitis, Allergic; Disease Models, Animal; Evans Blue; Guinea Pigs; Hypersensitivity, Immediate; Iris; Male; Ovalbumin; p-Methoxy-N-methylphenethylamine; Passive Cutaneous Anaphylaxis; Rabbits; Rats; Rats, Wistar; Uveitis

Narrowing of the airway lumen as a result of plasma exudation could augment airflow obstruction after allergen-induced bronchoconstriction. Because leukotrienes are putative mediators of bronchial asthma, the effects of a lipoxygenase inhibitor, VZ564 (N-hydroxy-N-(6-methoxy-3,4-dihydro-2- naphthylmethyl) urea. CAS 147495-99-6), on increased pulmonary permeability and bronchoconstriction during anaphylactic reaction were studied in guinea pigs and compared to the effects of the phosphodiesterase inhibitor theophylline. An anaphylactic reaction was induced by ovalbumin challenge (0.2 mg/kg i.v.) in passively sensitized and antihistamine (mepyramine)-pretreated guinea pigs; bronchoconstriction was measured as increased intratracheal pressure; lung vascular permeability was evaluated as extravasation of Evans blue dye up to 10 min after antigenic challenge. Ovalbumin challenge induced an increase in intratracheal pressure by 31 +/- 3 mmHg; the pulmonary permeability index was higher in ovalbumin-challenged versus saline (sham)-challenged guinea pigs (1.49 +/- 0.17 vs 0.56 +/- 0.04, p < 0.05). VZ564 and theophylline dose-dependently reduced increased pulmonary permeability and bronchoconstriction. VZ564 (10 and 46.4 mg/kg p.o., given 1 h before ovalbumin challenge) inhibited increased lung permeability by 42% and 95% and reduced bronchoconstriction by 61% at the higher dose. Theophylline (1 and 10 mg/kg i.v., given 10 min before ovalbumin challenge) diminished increased pulmonary permeability by 88% and reduced bronchoconstriction by 63% at the higher dose. In conclusion, the novel lipoxygenase inhibitor VZ564 inhibits after oral application important symptoms of asthma, namely bronchoconstriction and alveolar exudation of plasma in anaphylactic guinea pigs. The acute effects of VZ564 in this experimental model are comparable with the effects of the well known antiasthmatic substance theophylline.

Topics: Anaphylaxis; Animals; Asthma; Bronchoconstriction; Capillary Permeability; Guinea Pigs; In Vitro Techniques; Lipoxygenase Inhibitors; Lung; Male; Naphthalenes; Ovalbumin; Pulmonary Circulation; Theophylline; Urea

The possible occurrence of DIC in active systemic anaphylaxis was investigated in mice. Induction of active systemic anaphylaxis resulted in the development of DIC symptoms such as thrombocytopenia, prolongation of prothrombin time, hypofibrinogaemia, and elevated level of fibrinogen/fibrin degradation products. In addition, in histological examinations, massive congestion and cellular infiltration in pulmonary interstitia, and considerable haemorrhage in renal medullae were observed. All these changes were nearly completely prevented by pretreatment with platelet-activating factor (PAF) antagonist (BN 50739). Moreover, the same haematological and morphological changes were produced by a bolus injection of PAF. These data strongly suggest that DIC occurs in active systemic anaphylaxis and PAF plays a pivotal role in the development of DIC in anaphylaxis.

Topics: Anaphylaxis; Animals; Azepines; Disseminated Intravascular Coagulation; Male; Mice; Mice, Inbred BALB C; Ovalbumin; Platelet Activating Factor; Triazoles

The effect of 2-[2-[4-(diphenylmethyl)-1-piperadinyl]ethoxy] benzoic acid maleate (ZCR-2060) on passive systemic anaphylaxis (PSA) and antigen-induced immediate- and late-phase increase in airway resistance (Rrs) in either passively or actively sensitized guinea pigs were investigated. ZCR-2060 inhibited PSA in guinea pigs. ID50 values of ZCR-2060, ketotifen, terfenadine and cetirizine on PSA were 0.03, 0.02, 0.8 and 0.3 mg/kg, respectively, when administered orally 1 h before the antigen challenge. The protective effect of ZCR-2060 was observed until 12 h before the antigen challenge. Aeroantigen-induce immediate increase in Rrs in passively sensitized guinea pigs with and without metyrapone treatment was inhibited by ZCR-2060, ketotifen, terfenadine and cetirizine. In contrast, prednisolone did not affect the aeroantigen-induced immediate increase in Rrs in animals not treated with metyrapone, but significantly inhibited the metyrapone-induced enhanced immediate response. In actively sensitized animals, the immediate- and late-phase increases in Rrs were observed within 30 min and between 3 and 8 h after the aeroantigen challenge. Pretreatment with metyrapone accelerated both antigen-induced responses. ZCR-2060 (1 mg/kg) significantly inhibited both responses. Ketotifen (1 mg/kg), terfenadine (10 mg/kg) and prednisolone (10 mg/kg) significantly the inhibited the late-phase response, but did not affect the immediate-phase response. In contrast, Cetirizine (10 mg/kg) did not affect either response. The effect of ZCR-2060 on late-phase response was stronger than that of ketotifen, terfenadine and cetirizine, and was almost the same as that of prednisolone. These results suggest that ZCR-2060 has a potent protective effect on immediate- and late-phase increases in Rrs.

Topics: Airway Resistance; Anaphylaxis; Animals; Benzoates; Bronchi; Cetirizine; Female; Guinea Pigs; Ketotifen; Metyrapone; Ovalbumin; Piperidines; Prednisolone; Terfenadine

Rats of the Flinders sensitive line (FSL, selectively bred for their increased cholinergic activity and used as a genetic animal model of depression) were compared with their control counterparts, the Flinders resistant line, for their susceptibility to anaphylaxis and the response of small intestinal tissues to the muscarinic agonist, bethanechol. Following sensitization to ovalbumin (OA), rats of both lines were challenged in vivo either with 3 mg OA i.p. or with saline. In spite of the absence of line-related differences in IgE titers, FSL rats were more susceptible to the induction of anaphylactic shock as evidenced by (1) more pronounced mast cell degranulation; (2) a greater drop in rectal temperature; (3) higher hematocrit values; and (4) changes in gut function characterized by an elevation of basal short-circuit current and increased conductance (indicating increases in transport tone and permeability) of the tissues mounted in Ussing chambers. Thus, this study provides further evidence for a common cholinergic mechanisms in susceptibility to both allergies and depression.

Topics: Anaphylaxis; Animals; Antibodies; Atropine; Cell Degranulation; Depression; Disease Susceptibility; Electric Stimulation; Enteric Nervous System; Female; Intestinal Absorption; Intestine, Small; Male; Mast Cells; Muscarinic Antagonists; Ovalbumin; Parasympathetic Nervous System; Rats; Rats, Inbred Strains

The exposure of ovalbumin sensitized guinea-pig to an areosol of the specific antigen causes a respiratory crisis in approximately 100 s (dispnoea time) associated with a substantial increase in blood concentration of both histamine (from 27.5 +/- 1.8 ng/ml to 1570 +/- 26 ng/ml; n = 8) and thromboxane B2 (TXB2, from 0.52 +/- 0.03 ng/ml to 18.1 +/- 0.6 ng/ml; n = 8). The aerosol treatment of the animals (20 min) with furosemide (CAS 54-31-9, frusemide, FRU), nimesulide (CAS 51803-78-2, NIM), acetylsalicylic acid (CAS 50-78-2, ASA) and indometacin (CAS 53-86-1, INDO) at the concentrations of 1-3-10 and 30 mg/ml, before ovalbumin challenge, brought about an attenuation of anaphylactic response. The rank order of potency for the prolongation of dyspnoea time was FRU > NIM > ASA > INDO. In these experiments blood evaluation performed at the peak of the dyspnoea time for histamine concentration in the treated animals indicated that whereas FRU (ED25 = 2.14 mg/ml (1.97-2.38) and NIM (ED25 = 2.74 mg/ml (2.37-3.19)) were equiactive in reducing the release of histamine, ASA and INDO were devoid of this activity. On the contrary, the results obtained with ASA and INDO indicated a greater intrinsic activity in antagonizing TXB2 formation than that shown by the log-dose response curves of NIM and FRU. In another series of experiments the interaction of FRU with the other anti-inflammatory drugs in protecting guinea-pig from immune bronchoconstriction has been evaluated using the combination of two equiactive doses. The mixture considered were FRU+NIM, FRU+INDO and FRU+ASA. The results obtained indicated that FRU interacts positively with the three non-steroidal anti-inflammatory drugs in delaying the onset of the dyspnoeic crisis in guinea-pig. However, when FRU was combined with NIM the gain obtained (209%) appeared superior to that reached when FRU was combined with ASA (180%) or INDO (126%). Taken together these results suggest that non-steroidal anti-inflammatory compounds given by aerosol may represent a valid pharmacological intervention in protecting guinea-pig from anaphylactic bronchoconstriction.

Topics: Administration, Inhalation; Anaphylaxis; Animals; Anti-Inflammatory Agents, Non-Steroidal; Bronchoalveolar Lavage Fluid; Diuretics; Dose-Response Relationship, Drug; Drug Interactions; Furosemide; Guinea Pigs; Histamine Release; Male; Ovalbumin; Thromboxane B2

Intravenous injection of antigen is the fastest and most effective way of eliciting anaphylactic shock in previously sensitized rats. When intravenous injection is difficult or undesirable, subplantar challenge is a preferable alternative to the intraperitoneal route.

Topics: Aluminum Hydroxide; Anaphylaxis; Animals; Disease Models, Animal; Foot; Freund's Adjuvant; gamma-Globulins; Injections, Intradermal; Injections, Intramuscular; Injections, Intraperitoneal; Injections, Intravenous; Injections, Subcutaneous; Ovalbumin; Pertussis Vaccine; Rats; Rats, Inbred Lew

Rats were sensitized to chicken ovalbumin or human gamma-globulin by inoculation without adjuvants into the peritoneal cavity in the healing phase of a chemical peritonitis. This phase is associated with striking enhancement of lymphatic absorption. Small doses of antigen sensitized the rats for subsequent induction of anaphylaxis, but large doses were almost completely ineffective (inverse dose-response relation). When certain adjuvants were added to the antigen, both high and low doses of antigen were effective sensitizers for anaphylaxis. Neither high nor low doses of antigen sensitized if injected without adjuvants into the unprepared peritoneal cavity or by any other route. The effects of sensitization with low or high doses of antigen and the results of inoculation by effective and ineffective routes were interpreted in terms of the balance between absorption into the lymphatics and into the systemic blood circulation. Supplemental antigen inoculated into the systemic circulation was able to tip the balance against sensitization even when sensitization was done with potent adjuvants and by a favorable route. Splenectomy had little or no effect on suppression by supplemental antigen.

Topics: Absorption; Anaphylaxis; Animals; Depression, Chemical; Dose-Response Relationship, Immunologic; gamma-Globulins; Humans; Immunization; Injections, Intravenous; Lymphatic System; Male; Ovalbumin; Peritoneal Cavity; Pertussis Vaccine; Rats; Rats, Inbred Lew; Rats, Sprague-Dawley; Sodium Hypochlorite

Isolated hearts from ovalbumin sensitized guinea-pigs were perfused according to Langendorff. Ovalbumin injection decreased coronary flow. Left ventricular pressure amplitude and heart rate increased initially and decreased thereafter. Concomitantly, the liberation of histamine, prostaglandin F2 alpha, as well as the sum of leukotrienes C4/D4/E4/F4, measured in the perfusate by radioimmunoassay, was augmented. Staurosporine (1 microM), an inhibitor of protein kinases, did not influence the liberation of mediators in response to antigen challenge, but inhibited all mechanical responses. Infusion of phorbol myristate acetate, an activator of protein kinase C, into non-sensitized hearts decreased coronary flow and left ventricular pressure amplitude, but did not liberate mediators. Staurosporine (1 microM) abolished these mechanical responses. The results indicate that staurosporine suppresses cardiac anaphylaxis by blockage of mediator effects rather than by inhibition of liberation or formation of mediators.

Topics: Alkaloids; Anaphylaxis; Animals; Arachidonic Acids; Coronary Circulation; Dinoprost; Female; Guinea Pigs; Heart; Heart Rate; Hemodynamics; Histamine Release; In Vitro Techniques; Leukotrienes; Male; Ovalbumin; Radioimmunoassay; Staurosporine; Tetradecanoylphorbol Acetate; Ventricular Pressure

Anaphylaxis in the isolated guinea-pig heart was associated with a sudden release of histamine with a long-lasting release of nitrite (NO2-), an oxidation product of NO. NG-monomethyl-L-arginine (MeArg, 300 microM) increased the severity of cardiac anaphylaxis, as shown by the decrease in the coronary flow and by a prolonged duration of antigen-induced arrhythmias. Concomitantly, MeArg increased the release of histamine while decreasing the release of nitrite. Sodium nitroprusside (NaNP, 10(-5)-10(-4) M) reduced the severity of cardiac anaphylaxis by increasing coronary flow and shortening the duration of antigen-induced arrhythmias. Concomitantly, NaNP decreased the release of histamine while increasing the release of nitrite. In mast cells isolated from actively sensitized guinea-pigs, the release of histamine elicited by specific antigen was increased by MeArg and decreased by NaNP. In conclusion, endogenous and exogenous NO antagonizes the effect of vasoconstrictor mediators released after antigen challenge and plays a protective role in anaphylactic reactions "in vitro".

Topics: Amino Acid Oxidoreductases; Anaphylaxis; Animals; Arginine; Coronary Circulation; Guinea Pigs; Heart; Histamine Release; In Vitro Techniques; Male; Mast Cells; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase; Nitroprusside; Ovalbumin

Emedastine [1-(2-ethoxyethyl)-2-(4-methyl-1-homopiperazinyl)- benzimidazole difumarate] was evaluated for topical ocular anti-histaminic activity in histamine and antigen stimulated conjunctivitis models. Concentration-dependent inhibition of histamine induced vascular permeability changes occurring in the conjunctiva was observed when the time interval between topical ocular administration and histamine challenge ranged from 1 min to 8 hr. The calculated ED50 values obtained using intervals of 1 min, 30 min, 2, 4 and 8 hr were 0.0002%, 0.000035%, 0.0029%, 0.019% and 0.19%, w/v, respectively. Comparisons of relative potency 30 min post dosing between emedastine and other anti-histamines demonstrated that emedastine is equipotent to ketotifen, and 7, 7, 10, 10, 100, 357, 3333, and 5813 times more potent than brompheniramine, chlorpheniramine, clemastine, pyrilamine, levocabastine, pheniramine, diphenhydramine, and antazoline, respectively. Emedastine (0.1%) failed to significantly attenuate either serotonin or platelet-activating-factor induced vascular permeability changes indicating high selectivity for the histamine H1 receptor. In a passive conjunctival anaphylaxis model in guinea pigs, significant inhibition of the allergic response was observed following topical ocular administration of emedastine 5 min or 30 min prior to antigen challenge (ED50s 0.0046% and 0.00022%, respectively). These data clearly indicate that emedastine has potential as a topical ocular anti-histamine for treating allergic conjunctivitis.

Topics: Administration, Topical; Anaphylaxis; Animals; Benzimidazoles; Capillary Permeability; Conjunctiva; Conjunctivitis, Allergic; Drug Evaluation, Preclinical; Guinea Pigs; Histamine; Histamine H1 Antagonists; Male; Ophthalmic Solutions; Ovalbumin; Platelet Activating Factor; Rats; Rats, Sprague-Dawley; Serotonin

The study was made of aflatoxin B1 effect on guinea pig alimentary anaphylaxis to chicken ovalbumin (CO) and pasteurized cow milk (PCM), of CO-specific IgG antibody levels, some serum indices, sensitivity of the animals to LD50 histamine. In response to aflatoxin B1 alimentary anaphylaxis both to CO and PCM became more severe, lethality of the anaphylaxis to CO being in logarithmic relation to aflatoxin B1 dose (p < 0.05); specific IgG-antibodies to CO grew in number; serum total protein increased against unchanged levels of albumins; the activity of gamma-glutamyltransferase inhibited; histamine shock gained severity, its lethality being logarithmically related to the aflatoxin B1 dose. The discussion covers mechanisms underlying the animal allergic reactivity responses to aflatoxin B1.

Topics: Aflatoxin B1; Anaphylaxis; Animals; Blood Proteins; Chickens; Dietary Proteins; Drug Interactions; Food Hypersensitivity; gamma-Glutamyltransferase; Guinea Pigs; Immunoglobulin G; Lethal Dose 50; Male; Milk Hypersensitivity; Milk Proteins; Ovalbumin

Mice were fed for 2 mo diets having ratios of alpha-linolenate [18:3 (n-3)] to linoleate [18:2(n-6)] of < 0.01, 0.36, 1.0 and 3.9. Proportions of safflower seed oil and perilla seed oil were adjusted to obtain these ratios. The dietary alpha-linolenate to linoleate balance was reflected in the proportion of (n-3) and (n-6) highly unsaturated fatty acids with 20- and 22-carbon chains in spleen phospholipids, but the ratio did not affect the proportion of T lymphocyte subsets expressing CD4 and CD8 antigens in splenic leukocytes. The immunoglobulin (Ig) G and IgM responses against sheep red blood cells when estimated as plaque-forming cells present in spleen, were not affected significantly by the diets. However, the serum hemagglutinin titer was slightly but significantly higher in the high alpha-linolenate diet group [18:3(n-3)/18:2(n-6) = 3.9] than in the dietary group with 18:3(n-3) to 18:2(n-6) ratios of 0.36 and < 0.01. In contrast, the IgE antibody response against egg albumin, as well as the mortality from anaphylactic shock induced by a second challenge with antigen, was significantly lower in the high alpha-linolenate diet group [18:3(n-3)/18:2(n-6) = 3.9] than in the high linoleate diet [18:3(n-3)/18:2(n-6) < 0.01] group. These results, together with the reported suppressive effects of a high alpha-linolenate diet on the formation of lipid-derived allergic mediators, support the hypothesis that raising the (n-3) to (n-6) ratios of diets would be effective in reducing the severity of immediate-type allergic hypersensitivity.

Topics: alpha-Linolenic Acid; Anaphylaxis; Animals; Dietary Fats, Unsaturated; Fatty Acids; Hemagglutinins; Hypersensitivity, Immediate; Immunoglobulin E; Immunoglobulin G; Immunoglobulin M; Linoleic Acid; Linoleic Acids; Male; Mice; Mice, Inbred C3H; Mice, Inbred ICR; Ovalbumin; Phospholipids; Spleen; T-Lymphocyte Subsets

The aim of the study was to investigate if antigen-induced contraction of guinea pig lung parenchyma (GPLP) was an appropriate model for the study of antileukotriene drugs. Antileukotrienes have recently shown antiasthmatic effects in humans. Challenge of GPLP with a cumulatively increasing concentration of antigen evoked a graded contractile response. The antigen response could be divided into an immediate peak phase and a plateau phase of long duration. Histamine antagonism alone (mepyramine, H1, and metiamide, H2) had no effect on the response, whereas 5-lipoxygenase (5-lox) inhibitors (BAY x1005, MK-886 or BWA4C) depressed the plateau phase. When 5-lipoxygenase inhibition (BAY x1005 or MK-886) or cysteinyl-leukotriene receptor antagonism (ICI 198,615) was combined with histamine antagonism, there was a major attenuation of both components of the antigen response, leaving only a small residual response. In contrast, cyclooxygenase inhibition (diclofenac or indomethacin), antagonism of platelet-activating factor (WEB 2086) and thromboxane receptor antagonism combined with inhibition of thromboxane synthesis (BAY u3405 and CS-518) failed to inhibit the antigen response. In conclusion, cysteinyl-leukotrienes and histamine synergistically mediated the major part of the Schultz-Dale response in GPLP. The characteristics of GPLP anaphylaxis closely resembled those of antigen-challenged human bronci, supporting that antigen challenge of GPLP is a suitable model in experimental asthma research.

Topics: Anaphylaxis; Animals; Azepines; Guinea Pigs; Histamine; In Vitro Techniques; Indoles; Indomethacin; Leukotriene Antagonists; Leukotrienes; Lung; Male; Muscle Contraction; Ovalbumin; Platelet Activating Factor; Quinolines; Triazoles

The antigenic property of paclitaxel was examined using its protein mixtures (paclitaxel + OVA, paclitaxel + GSA, paclitaxel + RSA) in guinea pigs and mice in comparison with ovalbumin (OVA) and the protein conjugate of 4-aminoantipriyne (AAP). The following results were obtained: 1. When guinea pigs were sensitized with paclitaxel or paclitaxel + OVA emulsified with Freund's complete adjuvant, none of active systemic anaphylaxis (ASA), passive cutaneous anaphylaxis (PCA) and Schultz-Dale reaction were induced by challenge with paclitaxel or paclitaxel + GSA (guinea pig serum albumin). In the observation of active cutaneous anaphylaxis (ACA), no changes were observed in animals treated with paclitaxel alone as a sensitizing and/or a challenging antigen under the condition where slight delayed type hypersensitivity was elicited in animals sensitized with paclitaxel + OVA and challenged with paclitaxel + GSA. 2. When mice were sensitized with paclitaxel or paclitaxel + OVA adsorbed to alum. sera of these animals revealed a negative reaction in PCA using rats by challenge with paclitaxel or paclitaxel + RSA (rat serum albumin). 3. Protein bindings of paclitaxel with the above albumins were more than 40%. As shown above, paclitaxel was considered not to possess antigenic property under the experimental condition. In addition, the dose levels of paclitaxel employed in the present experiment were confirmed not to suppress the immune response to OVA.

Topics: Anaphylaxis; Animals; Antigens; Guinea Pigs; Hypersensitivity, Delayed; Immunization; Male; Mice; Mice, Inbred BALB C; Ovalbumin; Paclitaxel; Passive Cutaneous Anaphylaxis; Rats; Rats, Sprague-Dawley; Serum Albumin

Data in the literature concerning the role of macrophages in anaphylaxis are contradictory. In the present study, the effect of macrophage blockade induced by gadolinium chloride (GdCl3) on anaphylactic shock is investigated. Our observations show that GdCl3 prevents lethal anaphylactic shock in mice sensitized to ovalbumin. Gadolinium chloride given i.v. in a dose of 1 mg/100 g body weight 24 or 48 h before the elicitation of anaphylactic shock resulted in 80% survival, compared with the 43% survival in the control group. The same dose of this rare-earth metal salt also greatly reduced the mortality in mice sensitized with ovalbumin containing Bordetella pertussis vaccine, and similarly abrogated the symptoms of anaphylaxis, including the accumulation of serotonin and histamine in the liver. The results suggest that macrophages play an important role in mouse anaphylaxis.

Topics: Anaphylaxis; Animals; Gadolinium; Histamine; Kupffer Cells; Liver; Male; Mice; Mice, Inbred Strains; Ovalbumin; Phagocytosis; Serotonin

The potential antigenicity of the new cognition-enhancing agent nefiracetam (N-(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl)acetamide, DM-9384, CAS 77191-36-7) was investigated by tests for passive cutaneous anaphylaxis (PCA), systemic anaphylaxis (SA) and skin reaction in mice and guinea pigs. Mice were sensitized with nefiracetam (10-100 micrograms/animal) or nefiracetam-egg albumin (OA) mixture (10 micrograms/animal). No IgE antibodies to nefiracetam were detected in plasmas obtained from nefiracetam and nefiracetam-OA sensitized mice, indicating that nefiracetam has no immunogenicity or antigenicity eliciting potential. Guinea pigs were sensitized with nefiracetam (20-100 or 20 mg/kg) or nefiracetam-OA (2 mg/kg). No antibodies to nefiracetam were detected in the sera obtained from sensitized guinea pigs by PCA. Neither SA nor skin reaction was observed in the sensitized guinea pigs after the injection of challenge. These results suggest that nefiracetam possesses no antigenicity in mice and guinea pigs.

Topics: Anaphylaxis; Animals; Antigens; Female; Guinea Pigs; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Ovalbumin; Passive Cutaneous Anaphylaxis; Psychotropic Drugs; Pyrrolidinones; Rats; Rats, Sprague-Dawley; Skin Tests

Cholera toxin (CTX) is a potent oral adjuvant for the induction of mucosal IgA Ab responses protein Ags. We examined the Ab responses and allergic sensitization of several strains of mice to protein Ags, administered orally with CTX. The mice made strong IgA and IgG1 serum Ab responses, but little IgG2a Ab to Ags such as hen egg lysozyme (HEL) and OVA. However, when given a subsequent i.p. challenge with Ag alone, the same mice had immediate hypersensitivity reactions that included respiratory distress and death. Within 10 min of i.p. challenge, immunized mice had high levels of plasma histamine and extensive degranulation of mast cells in target tissues. These mice had detectable serum IgE Ab. Ag administered orally with the B subunit (CTB) of CTX did not sensitize mice. Intestinal tissues taken from these mice had Ag-specific ion-secretory responses in vitro, typical of intestinal anaphylaxis. Ag given s.c. without adjuvant could also sensitize for systemic and intestinal anaphylaxis. Sensitization with HEL given s.c. was dose dependent and correlated with a critical amount of HEL in the circulation. HEL was detected in the circulation after oral immunization, but CTX did not increase the uptake of HEL. Thus, oral immunization with a protein Ag in the presence of CTX can sensitize an animal for systemic and intestinal anaphylaxis. These results suggest a cautious approach to the use of CTX as an adjuvant in oral vaccines, and provide a new model to study immediate hypersensitivity reactions to intestinal Ag.

Topics: Administration, Oral; Anaphylaxis; Animals; Antigens; Cholera Toxin; Female; Hypersensitivity; Immunization; Immunoglobulin E; Immunoglobulin G; Intestines; Mice; Mice, Inbred C3H; Muramidase; Ovalbumin

The IgE-triggered release of mast cell mediators in response to antigen is thought to be the primary event in immediate hypersensitivity reactions such as systemic anaphylaxis. Although mast cells and basophils can be activated in vitro by non-IgE stimuli, it is not known whether these triggers lead to physiological changes in vivo. To investigate this possibility, we generated mice with a homozygous null mutation of the C epsilon gene. Such mice make no IgE, but produce other immunoglobulin isotypes normally. We report that despite the IgE deficiency, sensitized mutant mice become anaphylactic on antigen challenge and display tachycardia and pulmonary function changes similar to those seen in wild-type animals. These responses are accompanied by vascular leak, sharply elevated plasma histamine and rapid death. IgE-independent anaphylaxis does not depend on complement activation, but, as indicated in studies using genetically immunodeficient RAG-2- and SCID mice, does require a functional immune system. Such results clearly demonstrate that non-IgE pathways for hypersensitivity reactions exist in mice.

Topics: Anaphylaxis; Animals; Capillary Permeability; Cells, Cultured; DNA-Binding Proteins; Female; Hemodynamics; Histamine; Immunoglobulin E; Lung; Male; Mice; Mice, SCID; Ovalbumin; Proteins; Sequence Deletion; Spleen

Tracheal muscle strips isolated from guinea pigs passively sensitized with anti-egg albumin rabbit IgG were loaded with 86Rb as a K+ marker. The 86Rb efflux from the muscle tissue was measured after antigen exposure and the K(+)-channel subtypes involved in anaphylactic contraction were identified. The net 86Rb efflux was increased during antigen challenge. This increase was inhibited in Ca(2+)-free medium or in the medium of 40 mM of KCl, but not by 10 microM of glibenclamide or 20 mM of KCl. Decreased membrane potential and generation of action potentials were also observed during the anaphylactic contraction. As a comparison for antigen-induced 86Rb efflux changes, experiments using high concentrations of KCl were also performed. 86Rb efflux was increased depending on the KCl concentration. This increase was inhibited in Ca(2+)-free medium but not by 10 microM of glibenclamide. These results suggest that the K(+)-channel opening during IgG-mediated anaphylactic contraction was dependent on a decreased membrane potential due to 20-40 mM KCl. The subtype of the K(+)-channel involved is voltage-dependent K(+)-channel (Kv-channel), and Ca(2+)-activated K(+)-channel (KCa-channel) may also be involved in the 86Rb efflux change. The ATP-sensitive K(+)-channel (KATP-channel) was not involved in K(+)-channel opening during anaphylactic contraction.

Topics: Anaphylaxis; Animals; Calcium; Female; Guinea Pigs; Immunoglobulin G; In Vitro Techniques; Membrane Potentials; Muscle Contraction; Muscle, Smooth; Ovalbumin; Potassium Channels; Potassium Chloride; Rubidium Radioisotopes; Trachea

We examined the role of endothelium-derived nitric oxide during antigen-induced contraction in pulmonary arteries isolated from actively sensitized guinea pigs. Ovalbumin (10(-2) mg/ml)-induced contraction was not sustained, and tension returned to baseline within 15 min. Pretreatment with methylene blue (10(-5) M) increased both the amplitude and the duration of the contractile response in these tissues. At 15 min, tension remained elevated and was > 70% of the peak amplitude. Removal of the endothelium with saponin (200 micrograms/ml) increased the magnitude of the contraction by > 125%; however, the duration of the response was unaffected. After pretreatment with saponin, methylene blue no longer increased the amplitude of antigen-induced contraction but its effect on the duration was unchanged. Pretreatment with nitro-L-arginine methyl ester significantly increased the magnitude of the contraction in each of the tissues. These results suggest that the response of guinea pig pulmonary arteries to antigen is modulated by two types of endogenous vasodilators, endothelium-derived nitric oxide that inhibits the initial phase of the response and an endothelium-independent relaxing factor that is guanosine 3',5'-cyclic monophosphate dependent and attenuates the duration of anaphylactic contraction.

Topics: Anaphylaxis; Animals; Arginine; Endothelium, Vascular; Guinea Pigs; Hemoglobins; Male; Methylene Blue; NG-Nitroarginine Methyl Ester; Nitric Oxide; Ovalbumin; Pulmonary Artery; Saponins; Vasoconstriction; Vasodilation

The hypothesis that failure of hosts infected with Trypanosoma brucei to express type 1 hypersensitivity is related to this parasite's ability to down-regulate IgE production, and not to an innate lack of allergenicity of T. brucei antigens, was tested by studying anaphylaxis-induced changes in net epithelial ion transport in rats. Transport changes were quantified electrophysiologically in vitro, as a change in transmural short-circuit current when sensitized intestine was challenged with homologous antigen. Rats injected parenterally with trypanosome antigen elicited intestinal anaphylaxis in response to antigenic challenge, whereas the intestine of rats infected with T. brucei failed to respond. Infection with T. brucei also suppressed the anaphylactic response in rats sensitized to and challenged with ovalbumin and T. spiralis-derived antigens. In these cases suppression was related to the ability of T. brucei to block production of IgE, and not to the physiological failure of the epithelial response. However, in rats sensitized by infection with T. spiralis, neither the anaphylactic response nor IgE production were inhibited by T. brucei. Furthermore, intestinal mastocytosis normally associated with trichinosis was unaffected by the trypanosome infection. Results support the conclusion that the failure to express anaphylaxis in T. brucei-infected rats is due to the inhibition of IgE production and not to the lack of allergenicity of trypanosome antigens.

Topics: Anaphylaxis; Animals; Antigens, Helminth; Antigens, Protozoan; Chlorides; Immune Tolerance; Immunoglobulin E; Ion Transport; Jejunum; Male; Mast Cells; Ovalbumin; Rats; Rats, Sprague-Dawley; Trichinella spiralis; Trypanosoma brucei brucei

The ability of Tołpa Peat Preparation (TPP) to affect anaphylactic sensitization and mast cell secretory function was tested in BALB/c mice treated with TPP orally for 12 days. TPP in the doses of 20 and 50 mg/kg/day reduced histamine release from mouse peritoneal mast cells challenged with anti-IgE or concanavalin A in vitro. The treatment of mice with TPP from day 1 to day 12 of immunization with Ovalbumin (OA) absorbed on aluminium hydroxide gel resulted in a decrease of antigen-induced histamine release from mast cells of these mice in vitro and in decreased IgE antibody level in their sera. TPP introduced into OA-immunized mice showing developed IgE antibody response was less effective in decreasing anaphylactic histamine release from mast cells of these mice. In all experiments low doses of TPP used for oral treatment were more effective than high doses in inhibiting anaphylactic events in the mice.

Topics: Amino Acids; Anaphylaxis; Animals; Carbohydrates; Drug Combinations; Female; Histamine Release; Humic Substances; Immunoglobulin E; Mast Cells; Mice; Mice, Inbred BALB C; Ovalbumin; Rats; Rats, Wistar; Soil; Uronic Acids

Alteration of intestinal myoelectrical activity is a characteristic feature of food protein-induced intestinal anaphylaxis in the conscious rat. The motility changes induced by antigen challenge were appraised in egg-albumin-sensitized rats, chronically implanted with NiCr electrodes in the duodenojejunal wall. Intraduodenal infusion of egg albumin given to fasted sensitized rats triggered a disruption of the cyclic pattern of small intestinal motility lasting 79.1 +/- 23.3 min. The duration of the challenge effect on intestinal myoelectrical activity was significantly reduced by systemic capsaicin pretreatment (125 mg/kg) but to a lesser extent by perivagal capsaicin. Substance P (SP) antagonists (SP 4-11 and CP 96.345) and atropine were also able to shorten the duration of the antigen-challenge-induced alteration of intestinal motility. It is concluded that SP and capsaicin-sensitive afferent nerve endings play an important role in the intestinal anaphylaxis-induced disturbances of intestinal motility.

Topics: Afferent Pathways; Anaphylaxis; Animals; Atropine; Biphenyl Compounds; Capsaicin; Electromyography; Female; Gastrointestinal Motility; Intestine, Small; Muscle, Smooth; Ovalbumin; Rats; Substance P

A number of N-[4-[4-(1H-indol-3-yl)piperidinoalkyl]-2- thiazolyl]alkanesulfonamides (8--21) were synthesized and evaluated for their preventive effects on systemic anaphylaxis in guinea pigs. Structure-activity analysis revealed that methane- and ethanesulfonamide derivatives having a one to three methylene tether between the piperidine and thiazole rings exhibited potent activity but the introduction of a substituent on the indole part reduced the activity. Administration (100 mg/kg p.o.) of the four compounds 8, 9, 12, 13, together with ketotifen, oxatomide, terfenadine and azelastine as reference compounds, to mice revealed that only compound 8 caused no significant increase of the sleeping time induced by hexobarbital. In addition, compound 8 (10 mg/kg i.v.) did not change the electroencephalogram in conscious rabbits. These results led to the selection of N-[4-[4-(1H-indol-3-yl)piperidinomethyl]-2-thiazolyl]methanesulfon amide (8, FK613) for further development as a novel antiallergic agent. Clinical evaluation of FK613 is now in progress.

Topics: Anaphylaxis; Animals; Guinea Pigs; Hypersensitivity; Indoles; Male; Mice; Mice, Inbred ICR; Ovalbumin; Rabbits; Structure-Activity Relationship; Sulfonamides; Thiazoles

Intravenous injection of ovalbumin into actively and passively sensitized guinea-pig resulted in acute circulatory collapse. The plasma level of immunoreactive endothelin rose from 22 +/- 2 to 40 +/- 7 fmol/ml (n = 12, P < 0.01) and 29 +/- 5 fmol/ml (n = 12, P < 0.01) in actively and passively sensitized animals, respectively, within 5 min of antigen challenge, and it remained significantly higher in actively sensitized animals that survived for 15 min. The plasma immunoreactive endothelin level was inversely correlated with arterial blood pO2, but not with pH or pCO2, both in actively (rs = -0.585, n = 20, P < 0.05) and passively sensitized animals (rs = -0.558, n = 20, P < 0.05). When non-sensitized animals were bled (5 and 20 ml/kg body weight), the plasma immunoreactive endothelin level remained unchanged. These results suggest that the elevated plasma level of immunoreactive endothelin during anaphylactic shock is independent of hypotension, hypovolemia and respiratory insufficiency.

Topics: Anaphylaxis; Animals; Blood Pressure; Carbon Dioxide; Endothelins; Guinea Pigs; Hematocrit; Hydrogen-Ion Concentration; Male; Ovalbumin; Oxygen; Shock, Hemorrhagic

Rats were immunized by intraperitoneal injection of ovalbumin emulsified with Freund incomplete adjuvant, and then the effect of an intravenous challenge with ovalbumin on hepatic drug-metabolizing enzyme activities was examined. The cytochrome P-450 content and ethylmorphine N-demethylase, benzphetamine N-demethylase, arylhydrocarbon hydroxylase and 7-ethoxycoumarin O-deethylase activities significantly decreased in rats treated with ovalbumin compared with control groups treated with saline, whereas there was no significant reduction in cytochrome b5, NADPH-cytochrome c reductase and NADH-cytochrome c reductase.

Topics: Anaphylaxis; Animals; Liver; Male; Mixed Function Oxygenases; Ovalbumin; Pharmaceutical Preparations; Rats; Rats, Wistar

Altered intestinal motility and diarrhea are features of food protein-induced intestinal anaphylaxis in the conscious rat. These experiments were performed to determine the mediator(s) responsible for jejunal circular smooth muscle contraction during this response. Hooded-Lister rats were sensitized by intraperitoneal injection of 10-micrograms egg albumin, and controls were sham-sensitized with saline. Fourteen days later the contractility of the circular muscle in jejunal segments (mucosa intact) was examined in standard tissue baths in response to antigen (Ag) or other agents. While control and sensitized tissues contracted in similar fashion in response to stretch, bethanechol, histamine, or 5-hydroxytryptamine (5HT), Ag contracted only the segments of sensitized animals. The contractile response was: (1) specific to the sensitizing Ag, as bovine serum albumin did not induce contraction and (2) could be passively transferred with serum containing specific immunoglobulin E antibody (IgE-Ab). Concanavalin A, which degranulates both mucosal and connective tissue-type mast cells, and compound 48/80, which degranulates only connective tissue-type mast cells produced contractile responses. Ag-induced contraction was significantly inhibited by the mucosal and connective tissue-type mast cell stabilizer doxantrazole, but not the connective tissue mast cell stabilizer disodium cromoglycate. Diphenhydramine and cimetidine together significantly inhibited histamine-induced contraction, but failed to effect the Ag-induced contraction in sensitized tissues. While the contractile response to 5HT was reduced in the presence of methysergide (5HT1-receptor antagonist), cinanserin (5HT2-receptor antagonist), and ICS 205-930 (5HT3-receptor antagonist), only cinanserin significantly inhibited the contractile response to Ag. Indomethacin significantly inhibited Ag-induced contraction. Ag-induced contraction was resistant to atropine and tetrodotoxin.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Anaphylaxis; Animals; Cell Degranulation; Food Hypersensitivity; Gastrointestinal Motility; Immunoglobulin E; Jejunum; Mast Cells; Muscle Contraction; Muscle, Smooth; Ovalbumin; Prostaglandins; Rats; Serotonin

Intense acute stress, consequent to restraint, leads to a diminished production of IgE antiovalbumin antibodies in mice. The IgE content of sera from experimental or control animals was assayed by the enzyme-linked immunosorbent assay (ELISA) at days 8, 16, and 20 after immunization. The statistics revealed significant differences in the IgE level of the animals submitted to acute stress and home cage control animals on days 16 and 20 after immunization, but not on day 8.

Topics: Anaphylaxis; Animals; Arousal; Immune Tolerance; Immunoglobulin E; Male; Mice; Mice, Inbred A; Ovalbumin; Social Environment; Stress, Physiological

In vivo uptake of the probe 51Cr-labeled EDTA from the jejunum of egg albumin (EA)-sensitized rats was compared with controls at baseline and after intraluminal antigen challenge. Probe recovery in blood was 60-80% greater in sensitized animals during the baseline period, suggesting that sensitization resulted in increased intestinal permeability. Sensitized, but not control, rats demonstrated a 15-fold increase in 51Cr-EDTA uptake after intraluminal antigen; no change occurred with an unrelated protein. Macromolecular recovery was also enhanced in sensitized animals, since serum levels of immunoreactive EA were elevated 14-fold compared with controls. Antigen challenge was accompanied by biochemical (protease release) and morphological (reduced numbers) evidence of mast cell degranulation in sensitized rats. The neurotoxin tetrodotoxin (applied directly to ligated jejunal segments) inhibited EA-induced uptake of 51Cr-EDTA and antigen. In isolated jejunum from sensitized rats, tetrodotoxin reduced secretory responses to luminal, but not serosal, antigen. These results indicate that neural factors may influence the uptake of molecules from the gut lumen during intestinal anaphylaxis.

Topics: Anaphylaxis; Animals; Cell Membrane Permeability; Electric Conductivity; Electrophysiology; Epithelium; Hypersensitivity; Immunoglobulin E; Jejunum; Male; Membrane Potentials; Muscle, Smooth; Ovalbumin; Rats; Rats, Sprague-Dawley; Tetrodotoxin

1. Exogenous vasoactive intestinal polypeptide (VIP) infused into the pulmonary artery of isolated and ventilated lungs of guinea-pigs decreased, in a dose-dependent fashion (1.0-10.0 nmol), airway resistance and thromboxane B2 (TXB2, the stable hydrolysis product of TXA2) release in the perfusion medium. Prostacyclin (PGI2) synthesis, as reflected by the release of its stable hydrolysis product 6-oxo-PGF1 alpha, was unaffected. Pretreatment with the 5-lipoxygenase inhibitor BWA4c (3.5 x 10(-5) M) did not modify the bronchodilatory effect of VIP or its inhibitory action on TXB2 release. 2. Basal release of immunoreactive VIP from perfused lungs decreased from an initial value of 0.96 +/- 0.10 ng min-1 (mean +/- s.e.mean) in the first 2 min to an average of 0.58 +/- 0.10 ng min-1 in the following 15-20 min. 3. Antigen challenge with ovalbumin (0.1%) in sensitized lungs caused an anaphylactic reaction in 45% of tested lungs, concomitant with a 5 fold increase in both VIP and TXB2 release. Tetrodotoxin pretreatment (10(-6) M) reduced basal VIP release by > 80% and abolished the VIP increase observed during anaphylaxis, without modifying TXB2 release or the bronchoconstrictor response. 4. Indomethacin (10(-6) M) inhibited TXB2 synthesis and release by > 90%, delayed the bronchoconstrictor response and blunted the increased VIP release during lung anaphylaxis, without influencing basal VIP release. 5. The 5-lipoxygenase inhibitor BWA4c (3.5 x 10(-5) M) blunted the increase of TXB2 and VIP release from guinea-pig lung and attenuated the bronchoconstrictor response following ovalbumin challenge. 6. The administration of exogenous VIP as a continuous infusion (10-8 M) attenuated the bronchoconstriction and the release of cyclo-oxygenase metabolites following antigen challenge.7. Acetylcholine (10-6-l0-5 M) infused into the pulmonary artery induced a dose-dependent bronchoconstriction not associated with enhanced VIP or TXB2 release.8. The TXA2 mimetic U-46619 (0.1-1.0 nmol) caused dose-dependent increases in airway resistance,concomitant with an up to 10 fold increase in VIP release. VIP inhibited arachidonate-induced in vitro aggregation of washed rabbit platelets in a dose-dependent manner over a dose range 10-8 10-6 M.Despite the antiaggregatory effect of VIP, TXB2 and PGE2 synthesis was reduced only to a minor extent,and there was no redirection of arachidonate metabolism from TXA2 to PGE2, indicating that VIP does not act as a TX synthase inhibitor in vitro.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Acetylcholine; Anaphylaxis; Animals; Antigens; Benzeneacetamides; Bronchoconstriction; Guinea Pigs; Hydroxamic Acids; In Vitro Techniques; Indomethacin; Lipoxygenase Inhibitors; Lung; Male; Muscle, Smooth; Ovalbumin; Platelet Aggregation; Prostaglandin Endoperoxides, Synthetic; Prostaglandin-Endoperoxide Synthases; Rabbits; Radioimmunoassay; Tetrodotoxin; Thromboxane B2; Thromboxanes; Vasoactive Intestinal Peptide; Vasoconstrictor Agents

The interference of the platelet-activating factor (PAF) receptor antagonist compound, WEB 2170, on death caused by antigen in boosted or unboosted immunized mice was investigated. Death was triggered by the i.v. injection of ovalbumin into animals actively sensitized 14 or 21 days before and that received (boosted) or did not receive (unboosted), a second immunization 14 days later. No significant difference in the response to PAF (50 micrograms/kg) or to ovalbumin (500 micrograms/kg) was noted in boosted or unboosted mice in terms of mortality. WEB 2170 was equieffective to prevent death by PAF in non-sensitized or sensitized boosted or unboosted mice. The i.p. treatment with WEB 2170 (8-16 mg/kg) 1 h before the antigenic challenge prevented death due to antigen in unboosted or in boosted mice. Our results suggest that PAF is involved in the anaphylactic shock in unboosted and boosted mice. In addition, different from the anaphylactic reaction developed in the mouse paw, the participation of PAF in the anaphylactic shock caused by antigen is not dependent on the delivery of a booster injection.

Topics: Anaphylaxis; Animals; Azepines; Immunization, Secondary; Immunoglobulin E; Immunoglobulin G; Male; Mice; Ovalbumin; Platelet Activating Factor; Triazoles; Vaccination

An attempt of classical conditioning of anaphylaxis by odor was carried out, using actively sensitized guinea pigs with an inhalation of ovalbumin (OA). One month after sensitization, animals were divided into the conditioned group; group C, and the unconditioned group; group U, consisted of 6 animals, respectively. Dimethylsulfied (DMS: sulfur odor), was inhaled in group C as a conditioned stimulus with OA which is an unconditioned stimulus, while only OA was inhaled in group U. Four days after these procedures, saline was inhaled in group C and DMS was solely inhaled in group U in order to equalize the total inhaled dose of OA and DMS in both groups. These sessions were repeated once a week for seven weeks. After final sessions, all animals were inhaled DMS, saline and OA separately, and blood samples were drawn after each inhalation to measure plasma histamine levels. After an inhalation of DMS only, plasma histamine levels of group C and U were 47.5 +/- 9.7 and 25.7 +/- 1.2 ng/ml, respectively. In group C, plasma histamine levels were 32.9 +/- 4.7 at the inhalation of saline and 59.0 +/- 9.2 ng/ml at OA inhalation. Plasma histamine level after an inhalation of DMS only was significantly higher in group C than that in group U (p < 0.05). These results suggest that the conditional stimulus (DMS inhalation) may induce histamine release in the absence of any antigenic stimulus and support the evidence for mast cell-neuron interaction.

Topics: Anaphylaxis; Animals; Conditioning, Classical; Guinea Pigs; Histamine Release; Immunization; Male; Odorants; Ovalbumin; Sulfides

Topics: Anaphylaxis; Animals; Desensitization, Immunologic; Guinea Pigs; Histamine; Histamine Release; Immune Sera; Ovalbumin; Skin Tests

Anti-inflammatory properties of zinc protoporphyrin disodium (Zn-PP-2Na) were studied. Zn-PP-2Na exhibits anti-allergic action against type III and IV reactions (passive Arthus reaction in rats and tuberculin-induced footpad reaction in mice), but does not affect type I and II reactions (homologous passive cutaneous anaphylaxis in mice and reversed cutaneous anaphylaxis in rats). Zn-PP-2Na also clearly inhibits type II collagen-induced arthritis in mice. The agent inhibits general arthritis symptoms, anti-type-II collagen antibody production and type II collagen-induced delayed type hypersensitivity (DTH) in arthritic mice. Zn-PP-2Na, however, did not affect carrageenin-induced paw edema and histamine- and serotonin-induced skin reactions in rats. Zn-PP-2Na inhibits IL-1-induced mouse lymphocyte proliferation, but does not affect PMA-induced O2- generation from guinea-pig neutrophil. These results indicate that Zn-PP-2Na inhibits type II collagen-induced arthritis in mice due to the antagonism of IL-1 activity and the inhibition of DTH against type II collagen.

Topics: Anaphylaxis; Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis; Arthus Reaction; Ascaris; Collagen; Edema; Hypersensitivity; Interleukin-1; Lymphocytes; Male; Mice; Mice, Inbred BALB C; Mice, Inbred DBA; Ovalbumin; Oxygen Consumption; Passive Cutaneous Anaphylaxis; Protoporphyrins; Rats; Rats, Wistar; Skin Tests

The ability of Chelidonium majus L. alkaloids derivative Ukrain to induce an anaphylactic sensitization was tested on mice and guinea pigs. The levels of IgE antibody in the mouse sera, and IgG1a, IgG1b as well as IgE antibody levels in guinea pig sera, were evaluated by passive cutaneous anaphylaxis (PCA) tests. Ukrain alone or adsorbed on aluminium hydroxide gel (alum) introduced into BALB/c mice in several subcutaneous injections was unable to stimulate measurable anti-Ukrain IgE antibody response. Moreover, Ukrain introduced together with ovalbumin (OA) into mice in the course of immunization with OA induced lower anti-OA antibody response as compared to the response induced by OA alone. Ukrain adsorbed on alum and injected subcutaneously into guinea pigs did not induce measurable IgG1a, IgG1b and IgE antibody response. The present results suggest that the immunomodulating preparation Ukrain could be therapeutically safe at least as far its inability to induce anaphylaxis is concerned.

Topics: Adjuvants, Immunologic; Alkaloids; Anaphylaxis; Animals; Berberine Alkaloids; Female; Guinea Pigs; Immunoglobulin E; Immunoglobulin G; Male; Mice; Mice, Inbred BALB C; Ovalbumin; Passive Cutaneous Anaphylaxis; Phenanthridines

The inhibition of the haematological alterations and prevention of death due to systemic anaphylaxis after antigen challenge were investigated in rats after various drug treatments. The i.v. injection of ovalbumin (250 micrograms/kg) into actively sensitized rats induced marked thrombocytopenia and haemoconcentration within 5 min and significant leukocytosis within 30 min, lasting for 2 h after the challenge. Pretreatment with meclizine or terfenadine (15-30 mg/kg i.p.) inhibited antigen-induced haemoconcentration, whereas WEB 2086 (2-10 mg/kg i.p.) and PCA 4248 (5-10 mg/kg p.o.), two platelet-activating factor (PAF) antagonists, interfered with thrombocytopenia only. Azelastine (1-20 mg/kg p.o.) dose dependently inhibited antigen-induced haemoconcentration and thrombocytopenia but failed to block leukocytosis. Azelastine also inhibited the thrombocytopenia observed after the i.v. administration of PAF (4 micrograms/kg). Administration of ovalbumin at a dose of 1.5 mg/kg resulted in a lethal anaphylactic reaction in about 85% of the rats. Pretreatment with WEB 2086 (10 mg/kg i.p.), meclizine (30 mg/kg i.p.) or both increased the survival rate from 15 to 57, 68 and 87%, respectively. Azelastine alone (20 mg/kg p.o.) completely blocked the lethal reaction. It was concluded that the ability of azelastine to antagonize histamine and PAF is important for its effectiveness against anaphylactic shock.

Topics: Anaphylaxis; Animals; Azepines; Dihydropyridines; Dose-Response Relationship, Drug; Hematocrit; Histamine H1 Antagonists; Leukocyte Count; Male; Meclizine; Ovalbumin; Phthalazines; Platelet Activating Factor; Platelet Count; Rats; Rats, Inbred Strains; Terfenadine; Triazoles

The protective effects of two antihistamines and two anti-allergic drugs against anaphylactic paw edema were studied in immunized animals that had or had not received a booster injection of antigen. The injection of 1 or 10 micrograms/paw ovalbumin induced acute paw edema of similar intensity in both groups. The antihistamine meclizine and the mixed anti histamine/anti-5-HT antagonist cyproheptadine reduced the anaphylactic reaction by 55 and 84% respectively, in non-boosted animals and were less effective against edema induced by 1 microgram antigen in boosted animals. The effectiveness of these drugs was also reduced when boosted mice were challenged with 10 micrograms antigen, where meclizine and cyproheptadine inhibited edema by 31 and 59%, respectively. The anti-allergic compounds ketotifen and azelastine, although effective against allergic inflammation in non-boosted mice, had a reduced or no effect in boosted mice. Our results suggest that allergic edema is less sensitive to antihistamine and anti-allergic drugs in boosted mice, which may be accounted for by an increased role of other mediators.

Topics: Analysis of Variance; Anaphylaxis; Animals; Drug Interactions; Edema; Histamine H1 Antagonists; Immunization; Immunoglobulin E; Immunoglobulin G; Male; Meclizine; Mice; Ovalbumin

Effects of sensitizing antigen (ovalbumin) on various physiological and hepatic parameters were investigated in sensitized rats and isolated perfused livers derived from sensitized rats. Administration of ovalbumin (500 micrograms) to the portal venous circulation of sensitized but not nonsensitized rats resulted in a rapid and sustained decrease in systemic arterial pressure, characteristic of antigen-induced anaphylaxis, and pronounced increases in hepatic portal pressure and blood glucose concentration. These antigen-mediated alterations were similar to those observed in response to platelet-activating factor (PAF) (0.1 micrograms/kg) administration to rats and were inhibited significantly by specific PAF receptor antagonist WEB 2086 (250 micrograms/kg). Infusion of ovalbumin (3.8 micrograms/ml) into isolated perfused livers derived from sensitized rats resulted in significant increases in hepatic glucose output and portal pressure and decreases in oxygen consumption, as observed in response to PAF (0.28 nM) infusion into perfused livers. These hepatic responses to ovalbumin were antigen specific and were not observed in nonsensitized rat perfused livers. Hemodynamic and glycogenolytic responses to ovalbumin in perfused livers were inhibited significantly but less effectively than similar responses to PAF by infusion of WEB 2086 (500 nM) into livers. Coinfusion of indomethacin (2.8 microM) and nordihydroguariatic acid (1 microM) with WEB 2086 (500 nM) into perfused livers inhibited further hemodynamic but not glycogenolytic responses to ovalbumin. Infusion of nitric oxide (34 microM) into sensitized rat perfused livers prevented the hemodynamic and glycogenolytic responses to both ovalbumin and PAF. These observations provide evidence that hepatic glycogenolysis and vasoconstriction are stimulated during antigen-induced anaphylaxis and suggest that these responses are mediated in part by PAF.

Topics: Anaphylaxis; Animals; Antigens; Azepines; Eicosanoids; Epitopes; Female; Glycogen; Liver; Nitric Oxide; Ovalbumin; Platelet Activating Factor; Rats; Rats, Inbred Strains; Triazoles; Vasoconstriction

The antianaphylactic activity of inhaled frusemide was studied in ovalbumin-sensitized guinea-pigs. The exposure of the animals to frusemide aerosol (1% solution for 20 min) attenuated the respiratory response to ovalbumin challenge (aerosol 1% solution) and was associated with a significant reduction of blood histamine (70%; P less than 0.01) and thromboxane-B2 (35%; P less than 0.01) compared to control animals. Similar results were obtained in isolated lungs perfused via the trachea excised from ovalbumin-sensitized guinea-pigs exposed to frusemide aerosol (1% solution for 20 min). In this series of experiments frusemide significantly prevented the increase in tracheal perfusion pressure (45%; P less than 0.01) and the concomitant release into the pulmonary effluent of both histamine (75%; P less than 0.01) and thromboxane-B2 (39%; P less than 0.01). In another series of experiments, frusemide (1 x 10(-4) M) significantly reduced the immune release of histamine from mast cells of ovalbumin-sensitized rats. The inhibitory activity of frusemide was in the same range of potency (66%; P less than 0.01) as that of disodium cromoglycate (1 x 10(-4) M). These data taken together indicate that frusemide when given by inhalation prevents histamine release secondary to antigen-antibody reaction.

Topics: Administration, Inhalation; Anaphylaxis; Animals; Furosemide; Guinea Pigs; Histamine; Histamine Release; Immunization; Lung; Male; Ovalbumin; Radioimmunoassay; Rats; Thromboxane B2

Anaphylactic shock was induced in pentobarbital-anesthetized, mechanically ventilated Sprague-Dawley rats that had been sensitized 21 days earlier to crystallized ovalbumin. The sensitization was confirmed by passive cutaneous anaphylaxis test. Antigen challenge produced an immediate reduction in mean aortic pressure from 168 to 67 mm Hg within 1 minute after intravenous injection of ovalbumin. Plasma histamine increased from 4.5 to 128 ng/ml within 5 minutes after injection of antigen. There were no changes in airway or esophageal pressures after antigen challenge. Left ventricular diastolic pressure was increased, and contractility, as measured by the rate of change of left ventricular pressure (dP/dt), was decreased over an interval exceeding 90 minutes. When isolated, constant flow--perfused hearts from sensitized Sprague-Dawley rats were challenged with antigen, decreases in left ventricular function were observed associated with decreased positive and negative maximum rate of change of left ventricular pressure (dP/dtmax). This experimental model in the rat therefore demonstrated selective myocardial impairment with reduced inotropism and lusitropism after anaphylaxis.

Topics: Anaphylaxis; Animals; Antigens; Aorta; Cardiovascular System; Heart; Heart Ventricles; Histamine; In Vitro Techniques; Male; Myocardial Contraction; Ovalbumin; Perfusion; Pressure; Rats; Rats, Sprague-Dawley; Ventricular Function, Left

1. The effect of denervation on the anaphylactic contraction of the diaphragm from actively sensitized guinea pig has been studied. 2. The section of the phrenic nerve took place at cervical and thoracic levels. The sensitization of the animal took place several days before sectioning, simultaneously with denervation and after denervation. 3. The anaphylactic contractions were observed from the fourth day after thoracic denervation, and from the sixth day when denervation was in the cervical region. 4. The hypersensitivity to ACh in the denervated diaphragmatic muscle was present 24 hr after sectioning the phrenic nerve and reached its maximum 3-4 days after. 5. These results support the idea that denervation caused some changes in the membrane of the skeletal muscle fibres to allow the fixation of antibodies. These denervation changes are dependent on the length of the peripheral nerve left to degenerate. Anaphylactic contractions appeared earlier in those animals where phrenic nerve sections were closer to the diaphragmatic muscle.

Topics: Acetylcholine; Anaphylaxis; Animals; Diaphragm; Guinea Pigs; Histamine; Male; Muscle Denervation; Nerve Degeneration; Nerve Fibers; Ovalbumin; Phrenic Nerve

Effects of U-67590A, an analogue of methylprednisolone, on antigen-induced bronchoconstriction expressed as ventilation overflow were examined in ovalbumin-sensitized guinea pigs. When administered intravenously 17-18 hr before the challenge with antigen, U-67590A at doses of 10 and 30 mg/kg caused dose-dependent inhibition of increased ventilation overflow immediately after challenge. Death due to anaphylactic shock was markedly reduced by U-67590A. At 10 mg/kg (i.v.), U-67590A given 10 min before the challenge significantly inhibited the antigen-induced increase in ventilation overflow; the greatest inhibition seen 5-6 hr prior to the challenge. Pretreatment with 10 mg/kg FPL-55712 attenuated the increase in ventilation overflow during anaphylaxic shock. It is conceivable that inhibition of the leukotriene-mediated response is involved in the glucocorticoid-induced suppression of airway obstruction in anaphylaxis, and that inhibitory action of the glucocorticoid directly acting on the airway may account for the very fast onset of action.

Topics: Anaphylaxis; Animals; Antigens; Asthma; Bronchial Diseases; Chromones; Constriction, Pathologic; Dose-Response Relationship, Drug; Guinea Pigs; Male; Methylprednisolone; Ovalbumin; SRS-A; Time Factors

We studied the effect of NZ-107 in a number of animal models of anaphylactic bronchoconstriction. In conscious guinea pigs, pretreated with indomethacin, pyrilamine and propranolol, passively sensitized with heterologous anti serum, NZ-107 in doses of 10-30 mg/kg per os inhibited the aerosolized antigen-induced cough and collapse. NZ-107 in a high dose of 100 mg/kg per os significantly prevented aerosolized antigen-induced anaphylactic collapse, but not cough in actively or passively sensitized conscious guinea pigs and also significantly protected aerosolized histamine-induced collapse, but not cough in conscious guinea pigs. This compound had little inhibitory effect on aerosolized acetylcholine-induced cough and collapse. In anesthetized animals, the effect of NZ-107 on bronchoconstriction induced by intravenous administration of antigen and various agonists was examined by the method of Konzett and Rössler. In doses of 10-50 mg/kg per os, NZ-107 inhibited antigen-induced bronchoconstriction in anesthetized guinea pigs. NZ-107 when intravenously administered to the anesthetized guinea pigs inhibited not only leukotriene D4-induced bronchoconstriction, but also thromboxane A2 mimetic U-46619-, platelet-activating factor- and histamine-induced bronchoconstriction. In anesthetized rats, NZ-107 in a dose of 300 mg/kg per os tended to inhibit the antigen-induced bronchoconstriction, but this effect was not significant. These results indicate that NZ-107 acts as a spasmolytic agent which inhibits bronchial responses to antigens or various other bronchoconstrictors in animal models, suggesting that NZ-107 may be potentially beneficial in the treatment of bronchial asthma.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Acetylcholine; Anaphylaxis; Animals; Bronchoconstriction; Chromones; Disease Models, Animal; Dose-Response Relationship, Drug; Guinea Pigs; Histamine; Indomethacin; Injections, Intravenous; Male; Ovalbumin; Platelet Activating Factor; Propranolol; Prostaglandin Endoperoxides, Synthetic; Pyridazines; Pyrilamine; Rats; Rats, Inbred Strains; Regression Analysis; SRS-A

We previously demonstrated that the stomach is capable of mounting a type I hypersensitivity reaction to luminal antigen challenge. These findings imply that antigenically intact macromolecules cross the gastric mucosa. To test this hypothesis, rat gastric mucosa was mounted in Ussing chambers, and bovine serum albumin (BSA, 0.5 mg/ml) and 125I-labeled BSA (10 microCi) were added to mucosal fluids. After equilibration, serosal fluids were sampled for two 30-min periods, and fluxes of immunologically intact BSA (determined by an enzyme-linked immunosorbent assay) and total BSA (125I-BSA) were calculated under basal conditions and in the presence of NaF and colchicine, and at 4 degrees C. Additional experiments examined macromolecular permeability in sensitized-challenged tissues. Immunologically intact BSA (21.3 +/- 4.5 ng.30 min-1.cm-2) crossed the gastric mucosa as approximately one-fourth of the total BSA flux (78.2 +/- 7.5 ng.30 min-1.cm-2). The uptake of immunologically intact BSA was significantly reduced by NaF, an inhibitor of ATP production and endocytosis; colchicine, which inhibits polymerization of cytoskeletal microtubules; and at 4 degrees C, a general metabolic inhibitor. The transmural passage of antigen was not significantly altered by immunoglobulin E-mediated anaphylaxis. These findings indicate that intact protein antigens cross the gastric mucosa by an active, energy-dependent mechanism that uses the microtubular network.

Topics: Anaphylaxis; Animals; Autoradiography; Colchicine; Electric Conductivity; Enzyme-Linked Immunosorbent Assay; Gastric Mucosa; Immunization; In Vitro Techniques; Iodine Radioisotopes; Kinetics; Membrane Potentials; Ovalbumin; Rats; Rats, Inbred Strains; Serum Albumin, Bovine; Sodium Chloride

1. To investigate the role of platelet activating factor (PAF) in the immediate asthmatic response, we examined the bronchial reactivity to histamine after administration of PAF to guinea-pigs or antigen challenge to passively sensitized guinea-pigs. 2. A bolus injection of PAF (20-40 ng kg-1), which did not cause a significant increase in intrathoracic pressure (ITP), augmented the bronchial response to histamine almost 8 fold. This airway hyperreactivity was observed even 1 min after PAF treatment. 3. A subthreshold dose of antigen (0.01 mg kg-1, i.v.) also provoked hyperreactivity to histamine, which became significant 6 and 11 min after the antigen treatment. 4. The specific PAF-antagonists, SM-10661 and CV-6209 (i.v.) dose-dependently inhibited both PAF- and antigen-induced airway hyperreactivities to histamine. 5. These results suggest that PAF plays an important role in antigen-induced acute airway responses by augmenting the activities of spasmogens.

Topics: Anaphylaxis; Animals; Asthma; Bronchi; Guinea Pigs; Histamine; Male; Ovalbumin; Platelet Activating Factor; Platelet Count; Pyridinium Compounds; Respiratory Function Tests; SRS-A; Thiazoles; Thiazolidines

Experimentally-induced type 1 hypersensitivities were induced in normal dogs to either ovalbumin or Ascaris antigen. In vitro and in vivo cell-mediated immune responses were measured before sensitization and again at 1 and 6 days after induction of anaphylaxis by intravenous challenge with antigen. Histamine-modulated lymphocyte functions, such as histamine-induced suppression, histamine co-mitogen induced blastogenesis and the in vivo cutaneous responses to intradermally injected mitogens decreased post anaphylaxis. Spontaneous suppression of the autologous mixed-lymphocyte reaction increased post anaphylaxis. Lymphocyte blastogenic response to Concanavalin A (Con A) decreased at 6 (but not at 1) days post anaphylaxis probably due to a mediator other than histamine. Blastogenesis of 24 h preincubated cells by suboptimal concentration of Con A, declined post anaphylaxis, but Con A-induced suppression was not significantly altered. Dogs with atopic dermatitis have some altered cell-mediated immune responses. Altered histamine-induced and spontaneous suppression, histamine suppression of mitogenesis and decreased contact sensitivity observed in this experimental type 1 hypersensitivity mimicked that of atopic dogs. Increased cutaneous response to mitogens observed in atopic dogs was not reproduced in the type 1 hypersensitive dogs. These findings suggest some of the altered cell-mediated immune functions observed in dogs with atopic dermatitis result from type 1 hypersensitivity. The other abnormalities may be intrinsic to the atopic state.

Topics: Anaphylaxis; Animals; Antigens, Helminth; Ascaris; Concanavalin A; Dog Diseases; Dogs; Drug Synergism; Female; Histamine; Immune Tolerance; Immunity, Cellular; Immunization; Intradermal Tests; Lymphocyte Activation; Lymphocytes; Male; Ovalbumin

In isolated perfused ovalbumin-sensitized guinea-pig hearts modulating effects of nitric oxide (NO) on cardiac function and eicosanoid release were investigated. While the NO-donor SIN-1 exhibited a protective effect during cardiac anaphylaxis, inhibition of NO biosynthesis by NNA or NMMA aggravated anaphylactic changes of cardiac functions. Exogenous and endogenous NO seems to functionally antagonize the effects of vasoconstrictor mediators released during the anaphylactic reaction. In addition, inhibition of cysteinyl-leukotriene (cys-LT) release could contribute to the protective effect of SIN-1 observed.

Topics: Anaphylaxis; Animals; Arginine; Coronary Circulation; Eicosanoids; Guinea Pigs; Heart; Heart Rate; In Vitro Techniques; Male; Molsidomine; Myocardium; Nitroarginine; omega-N-Methylarginine; Ovalbumin

1. BN 52021, an antagonist of platelet activating factor (PAF), was inactive against bronchoconstriction in guinea-pigs sensitized with low amounts of ovalbumin (OA) injected twice, at a 14 day interval and challenged i.v. 7 days later. 2. Serum IgG titers increased for 7 weeks after the booster injection at day 14 and returned to low levels at day 96. 3. Administered by the intratracheal (i.t.) route at 1 mg, BN 52021 failed to inhibit bronchoconstriction induced by the i.t. administration of OA to guinea-pigs tested 7, 28, 56 and 84 days after the booster injection, even when the titers of circulating IgG had declined with time. BN 52021 was also inactive against bronchoconstriction in guinea-pigs boosted at day 98 and tested 7 days later and against contractions and thromboxane (Tx) B2 and histamine release induced by OA-challenged parenchymal lung strips from the boosted guinea-pigs. 4. Sensitized unboosted guinea-pigs displayed reduced IgG serum titers. Used 21 or 70 days after the sensitizing injection, they did develop bronchoconstriction upon the i.t. instillation of OA, which was blocked by BN 52021. The latter also inhibited OA-induced contractions of lung parenchymal strips from these unboosted guinea-pigs. 5. When boosted and non-boosted guinea-pigs received OA i.t. and bronchoalveolar lavage fluid was collected 10 min later, the number of eosinophils increased markedly in boosted, but not in non-boosted guinea-pigs. 6. The booster injection of antigen thus modifies the response of the lung and PAF appears to be relevant for antigen-induced bronchoconstriction in unboosted animals, but loses its major role following the booster injection.

Topics: Anaphylaxis; Animals; Bronchoconstriction; Diterpenes; Female; Ginkgolides; Guinea Pigs; Histamine Release; Immunization, Secondary; In Vitro Techniques; Lactones; Lung; Male; Ovalbumin; Platelet Activating Factor; Thromboxane B2

We have purified and characterized the guinea pig eosinophil chemotactic factor of anaphylaxis (ECF-A), an activity previously described in diffusates from sensitized lung challenged with specific Ag that appeared to selectively attract eosinophils from mixed leukocyte populations. Time course studies showed that the release of ECF-A from challenged presensitized guinea pig lung fragments closely paralleled the release of immunoreactive leukotriene B4 (iLTB4) and histamine. However, the majority of ECF-A (greater than 80%) and iLTB4 (greater than 79%) was extractable with the lipid fraction from the methanol wash of Sep-Pak-extracted diffusate, whereas histamine remained in the aqueous phase. A comparable neutrophil chemotactic activity was also found in the methanol extracts of the anaphylactic diffusates. By using a combination of HPLC and specific RIA, greater than 60% of ECF-A was attributable to LTB4. A second eosinophil chemotactic activity was also identified and coeluted (on both reverse phase and straight phase HPLC) with the synthetic standard 8(S),15(S)-dihydroxy-5,9,11,13(Z,E,Z,E)eicosatetraenoic acid (8(S),15(S)-diHETE). This was confirmed as 8(S),15(S)-diHETE by gas chromatography-mass spectrometry. Platelet-activating factor and histamine had negligible activity for guinea pig eosinophils, compared with synthetic LTB4 (p less than 0.05, 10(-9) and 10(-8) M; p less than 0.01, 10(-7) to 5 x 10(-6) M). In addition, synthetic 8(S),15(S)-diHETE had 3 times less activity than LTB4 at optimal chemotactic concentrations (10(-6) and 10(-7) M, respectively). Thus, guinea pig ECF-A appears to be largely attributable to lipoxygenase products of arachidonic acid, namely LTB4 and 8(S),15(S)-diHETE. Because guinea pig ECF-A was equally active on neutrophils (greater than 96% purity), it can no longer be considered a selective eosinophil chemoattractant.

Topics: Anaphylaxis; Animals; Chemotactic Factors, Eosinophil; Chromatography, High Pressure Liquid; Female; Gas Chromatography-Mass Spectrometry; Guinea Pigs; Histamine; Leukotriene B4; Ovalbumin

We investigated the changes in beta-adrenoceptor responses induced in guinea-pig tracheal and cardiac tissues by the anaphylactic reaction. Antigen aerosol challenge in sensitized guinea-pigs resulted in a marked reduction in adrenaline relaxation in isolated trachea ex vivo. The isoprenaline effect was also slightly decreased by antigen exposure, suggesting a possible impairment of tracheal beta-adrenoceptor function. On the other hand, the chronotropic and inotropic activity of adrenaline in isolated atria was not modified by the anaphylactic shock, suggesting a specific involvement of lung beta-adrenoceptors in the allergic reaction.

Topics: Aerosols; Anaphylaxis; Animals; Antigens; Epinephrine; Guinea Pigs; Heart; Heart Rate; In Vitro Techniques; Isoproterenol; Lung; Male; Muscle Relaxation; Muscle, Smooth; Myocardial Contraction; Ovalbumin; Receptors, Adrenergic, beta; Trachea

A new model of active anaphylactic reaction in mice was developed. The edematogenic reaction appeared 5 min after the intraplantar injection of ovalbumin, peaked at 30 min after the antigenic challenge, and decreased thereafter. Using the non-steroidal, anti-inflammatory agents indomethacin and aspirin, we found that cyclooxygenase products do not participate in the reaction. In contrast, vasoactive amines appear to be involved, because meclizine and methysergide reduced the edema. Dexamethasone, BW755C, LY 171883 and WEB 2170 effectively interfered with the edematogenic reaction, which suggests that lipid mediators such as leukotrienes and PAF play a role in the active anaphylactic response.

Topics: 4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; Acetophenones; Anaphylaxis; Animals; Aspirin; Azepines; Cimetidine; Dexamethasone; Edema; Male; Meclizine; Methysergide; Mice; Ovalbumin; Platelet Activating Factor; Platelet Membrane Glycoproteins; Prednisolone; Receptors, Cell Surface; Receptors, G-Protein-Coupled; Tetrazoles; Triazoles

The heart is a target organ of anaphylaxis. In isolated perfused hearts, an anaphylactic reaction is characterized by arrhythmias, coronary constriction and severe impairment of ventricular contractile force. Various mediators such as PAF, thromboxane A2 and leukotrienes are responsible for anaphylactic coronary constriction and negative inotropic effects. The cardiac effects of anaphylactic histamine release are related to the stimulation of two antagonistic receptor types. Histamine induces atrioventricular conduction delay and constriction of the epicardial coronary vessels via H1-receptor stimulation. H2-receptors, however, mediate coronary vasodilation and an increase in heart rate and myocardial contractility. It may therefore be concluded that administration of histamine H2-receptor antagonists is disadvantageous. During anaphylactic states, the cardiodepressive effects of the other mediators of anaphylaxis are unmasked, resulting in a sustained coronary constriction and impairment of myocardial contractility. To verify this speculation, we investigated the effects of H1- and H2-receptor antagonists on cardiovascular function of guinea pigs during systemic anaphylaxis. In guinea pigs, sensitization was produced by subcutaneous application of ovalbumin. Fourteen days after sensitization, the effects of an intravenous infusion of ovalbumin were tested in the anesthetized artificially ventilated guinea pigs. The renewed administration of the antigen induced severe cardiac dysfunction. Within a few minutes, cardiac output markedly decreased and left ventricular end-diastolic pressure increased significantly, indicating left ventricular pump failure. In the same time range, ECG recordings uniformly showed signs of acute myocardial ischemia. In addition, arrhythmias occurred in terms of an atrioventricular block.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Anaphylaxis; Animals; Astemizole; Benzimidazoles; Blood Pressure; Cardiac Output; Cardiovascular System; Electrocardiography; Famotidine; Female; Guinea Pigs; Histamine H1 Antagonists; Histamine H2 Antagonists; Kinetics; Male; Myocardial Contraction; Ovalbumin; Stroke Volume

In vivo anaphylaxis is associated with respiratory distress and cardiovascular failure. The present investigation was designed to further characterize respiratory and cardiac anaphylactic events. In guinea pigs, sensitization was produced by subcutaneous application of ovalbumin together with Freund's adjuvant. Fourteen days after sensitization, the effects of an intravenous infusion of ovalbumin were tested in the anesthetized artificially ventilated guinea pigs. The renewed application of the antigen induced an initial increase of left ventricular pressure which was followed by a rapid decrease 5 min after antigenic challenge. Enddiastolic left ventricular pressure increased within 3 min, thus indicating left ventricular pump failure. In the same time range, ECG recordings uniformly showed signs of acute myocardial ischemia. In addition, heart rate steadily decreased. All animals died within 15 min. Simultaneously with cardiac anaphylactic malfunction, severe arterial hypoxia and carbon dioxide retention occurred, revealing respiratory distress. Histamine is known as a potent bronchoconstrictor via histamine H1-receptor stimulation. Administration of H1-receptor antagonists to improve respiration may therefore provide further information on the contribution of pulmonary malfunction to anaphylactic cardiovascular shock. Therefore, additional experiments were performed with sensitized guinea pigs pretreated with the histamine H1-receptor blocker mepyramine. In these experiments the antigenic challenge induced a dissociation of cardiac and respiratory manifestation of anaphylaxis. Despite inhibition of hypoxia and carbon dioxide retention, left ventricular pump failure and occurrence of myocardial ischemia were delayed but not suppressed. It is concluded that histamine is an important mediator of anaphylactic respiratory distress. However, vasoactive anaphylactic mediators other than histamine are primarily involved in anaphylactic cardiac malfunction occurring during the later phase of systemic anaphylaxis.

Topics: Anaphylaxis; Animals; Blood Gas Analysis; Electrocardiography; Female; Guinea Pigs; Heart; Heart Ventricles; Histamine; Histamine H1 Antagonists; In Vitro Techniques; Male; Ovalbumin; Pyrilamine; Respiration

The action of theophylline was studied on the inflammatory reaction obtained in bronchoalveolar lavage fluid 24 h after an active anaphylactic shock had been induced by ovalbumin inhalation in conscious sensitized guinea-pigs. The compound was administered twice by intraperitoneal administration after the anaphylactic reaction at a dose of 50 mg kg-1. When the guinea-pigs were sensitized by intramuscular injection of 30 mg kg-1 ovalbumin or by ovalbumin aerosol, theophylline reduced the number of eosinophils and mononuclear cells in the fluid. When animals were sensitized by intramuscular injection of 30 mg kg-1 ovalbumin mixed with Freund's complete adjuvant, treatment with the xanthine derivative decreased only the number of eosinophils. In the three models theophylline did not modify significantly the number of neutrophils. Thus theophylline always reduced pulmonary eosinophilia irrespective of the mode of sensitization used to induce anaphylactic shock.

Topics: Aerosols; Anaphylaxis; Animals; Bronchitis; Bronchoalveolar Lavage Fluid; Eosinophils; Guinea Pigs; Injections, Intramuscular; Lung; Male; Neutrophils; Ovalbumin; Theophylline

The response to antigen (trinitro-phenyl-haptenized ovalbumin) and the modulatory role of several antiallergic drugs was studied in isolated hearts from actively sensitized rats. Antigen induced a triphasic effect on coronary flow (CF) and left ventricular pressure (LVP) characterized by short-term increase (0-1.5 min = phase 1) and a severe decrease (1.5-7.5 min = phase 2) followed by a less pronounced long-lasting decrease (7.5- greater than 20 min = phase 3). The first phase was accompanied with a substantial release of 5-hydroxytryptamine (5-HT), histamine, and leukotrienes measured in cardiac effluents. The histamine2 (H2)-receptor antagonist cimetidine (60 microM) reversed the antigen-induced increase in CF to a decrease. In contrast, H1-receptor blockade by mepyramine (6 microM) had no effect. Methysergide (10 microM) and ketotifen (0.1 microM) evoked a mild suppression during all three phases. Indomethacin (10 microM) was almost inactive while tolfenamic acid (1 microM) was slightly active in this respect during phase 2. Addition of the 5-lipoxygenase inhibitor AA 861 (1 microM) resulted in complete suppression of the antigen-induced decrease in CF. The leukotriene antagonist FPL 55712 (5 and 50 nM) evoked a dose-dependent suppression with respect to the anaphylactic phases 2 and 3. A similar reduction was obtained with sodium cromoglycate (1 mM). AA 861, FPL 55712, and sodium cromoglycate also suppressed the antigen-induced decrease in LVP. The antigen-induced histamine release was not affected by the aforementioned drugs. Our results provide evidence that H2-receptor blockade during cardiac anaphylaxis enhances coronary constriction and may be detrimental in this condition. On the other hand, leukotriene antagonists and 5-lipoxygenase inhibitors may exert beneficial effects during cardiac anaphylaxis. Further experiments in this area are needed to clarify the precise role of mast cell-generated mediators in cardiac anaphylaxis possibly leading to new therapeutic approaches in this life-threatening disorder.

Topics: Anaphylaxis; Animals; Antigenic Modulation; Antigens; Chromatography, High Pressure Liquid; Coronary Circulation; Heart; Histamine; Histamine H1 Antagonists; Histamine H2 Antagonists; Histamine Release; Hypersensitivity; Immunoglobulin E; In Vitro Techniques; Leukotrienes; Lipoxygenase Inhibitors; Male; Myocardium; o-Phthalaldehyde; Ovalbumin; Radioimmunoassay; Rats; Rats, Inbred Strains; Serotonin; Spectrometry, Fluorescence

Our accompanying paper demonstrated that endothelin-1 (ET-1 constricts guinea pig airways directly and indirectly through mediators such as histamine and arachidonate metabolites. In order to exclude the role of mast cells in bronchoconstriction, we sensitized guinea pigs and challenged them in vitro with an antigen (ovalbumin). In the postanaphylactic trachea, ET-1 caused a transient relaxation followed by constriction. Such relaxation by ET was also observed in the tracheas constricted with carbamylcholine. The relaxation was completely blocked by nordihydroguaretic acid and AA861, lipooxygenase inhibitors, but not by indomethacin, a cyclooxygenase inhibitor, and FPL 55712, a leukotriene antagonist. Because the relaxation was not affected even in the presence of methylarginine, an inhibitor of NO synthesis, and superoxide dismutase, an enzyme for destroying NO radical, we concluded that ET-1 induces the relaxation of the tracheal muscles by producing lipooxygenase products, probably hydroperoxides of arachidonic acid.

Topics: Anaphylaxis; Animals; Arachidonate 5-Lipoxygenase; Arachidonic Acid; Cyclooxygenase Inhibitors; Endothelins; Female; Guinea Pigs; In Vitro Techniques; Lipoxygenase Inhibitors; Muscle Contraction; Muscle Relaxation; Muscle, Smooth; Nitric Oxide; Ovalbumin; Superoxide Dismutase; Trachea

Data in the literature concerning the role of macrophages in anaphylaxis are contradictory. In the present study the effect of macrophage blockade induced by gadolinium chloride (GdCl3) on anaphylactic shock was investigated. Our observations show that GdCl3 prevents the lethal anaphylactic shock of mice sensitized to ovalbumin. GdCl3 given i.v. in a dose of 1 mg/100 g body weight 24 or 48 h before the elicitation of anaphylactic shock resulted in 90% survival, compared to the 43% survival in the control group. The same dose of this rare earth metal salt also greatly reduced the mortality in mice sensitized with ovalbumin containing Bordetella pertussis vaccine, and the symptoms of anaphylaxis including the accumulation of 5-hydroxytryptamine in the liver. Our results suggest that macrophages play an important role in anaphylaxis.

Topics: Anaphylaxis; Animals; Gadolinium; Liver; Macrophages; Male; Mice; Ovalbumin; Pertussis Vaccine; Serotonin

There have been many reports of the immunomodulatory effects of stress, but the influence of stress on anaphylaxis has been given little attention till now. In this study we investigated the influence of tail-shock stress on the course of anaphylactic shock (AS) in the rat. For this purpose, rats were sensitized to ovalbumin and subjected to stress procedure before the induction of AS. In the first series of experiments we used chronic (4 day) stress consisted of 80 inescapable tail shocks delivered at the same time each day. Anaphylactic shock was induced 24 hours later by intraperitoneal injection of 3 mg of ovalbumin. Results showed that stressed rats exhibited lower intensity of three investigated parameters of AS: clinical signs, hematocrit values, and drop of rectal temperature. In order to investigate whether acute stress procedure could also influence course of AS, rats were given various shock doses of ovalbumin immediately after the end of acute (1 day) tail-shock stress. Anti-anaphylactic effect of acute stress was demonstrated to be dose-dependent: the greatest protective effect was in animals that received the highest shocking dose of ovalbumin. Finally, we examined the duration of protective effect of acute inescapable tail shocks on AS, and these results showed that observed anti-AS phenomenon disappears 72 hours after the end of acute stress session.

Topics: Anaphylaxis; Animals; Body Temperature; Electroshock; Hematocrit; Male; Ovalbumin; Rats; Rats, Inbred Strains; Stress, Psychological

Topics: Anaphylaxis; Animals; Chickens; Cytochrome P-450 Enzyme System; Food Hypersensitivity; Guinea Pigs; Male; Methylcholanthrene; Microsomes, Liver; Ovalbumin

The effects of the platelet-activating factor (PAF) antagonist, E6123, on anaphylactic responses in guinea pigs and mice were investigated. E6123 inhibited i.v. antigen (Ag)- or inhaled Ag-induced bronchoconstriction in passively and actively sensitized guinea pigs after oral administration at 3 and 10 micrograms/kg, respectively. E6123 inhibited Ag inhalation-induced airway hyperreactivity in guinea pigs after oral administration at 30 micrograms/kg. E6123 protected mice from anaphylactic death with an ED50 value (p.o.) of 7 micrograms/kg. The inhibitory effects of E6123 described above were very potent compared to those of the PAF-antagonists WEB2347 and Y-24180. The present results suggest that E6123 may be beneficial for the treatment of asthma, a condition in which PAF is assumed to be involved.

Topics: Administration, Inhalation; Anaphylaxis; Animals; Antigens; Asthma; Azepines; Guinea Pigs; Male; Mice; Mice, Inbred ICR; Ovalbumin; Platelet Activating Factor; Propranolol; Pyrilamine; Triazoles

In anaphylactic shock, SR 27417, the first member of a newly developed series of PAF (platelet-activating factor) antagonists, inhibited in a dose-dependent manner the lethal effect of antigen (ovalbumin) rechallenge in actively sensitized mice. It protected mice when given i.v. 5 min before ovalbumin challenge (ED50 = 50 micrograms/kg) or when given p.o. 1 h before ovalbumin administration (ED50 = 1.25 mg/kg). After i.v. or oral administration, SR 27417 (2.5 and 10 mg/kg, respectively) greatly improved the survival rate of mice after antigen challenge and had an extremely long duration of action (48 and 30 h, respectively). Similarly, i.v. or oral doses of SR 27417 afforded in mice complete protection against endotoxin-induced lethality (ED50 values were 100 and 150 micrograms/kg, respectively). SR 27417 (1 mg/kg) inhibited endotoxin-induced death in mice with impressive oral or i.v. durations of action of 66 and 110 h, respectively. These results confirm that PAF plays a major role in anaphylactic and endotoxin-induced shock and that SR 27417 may be an effective preventative drug.

Topics: Anaphylaxis; Animals; Azepines; Dose-Response Relationship, Drug; Endotoxins; Escherichia coli; Male; Mice; Mice, Inbred Strains; Ovalbumin; Platelet Activating Factor; Shock, Septic; Thiazoles; Triazoles

The effect of SM-10661, a selective antagonist of platelet-activating factor (PAF), on passive anaphylactic bronchoconstriction was examined in guinea pigs. A challenge of ovalbumin to passively sensitized guinea pigs induced bronchoconstriction, which peaked at 4 min. When SM-10661 was administered intravenously 2 min before ovalbumin challenge, bronchoconstriction was inhibited dose-dependently with an ID50 of 68 mg/kg. In guinea pigs pretreated with 15 micrograms/kg mepyramine which is a suboptimal dose, antigen-induced bronchoconstriction peaked at 4-6 min, but was inhibited by SM-10661 with an ID50 of 21 mg/kg. When guinea pigs were pretreated intravenously with 2.5 mg/kg mepyramine, 1 mg/kg indomethacin and 0.01 mg/kg propranolol, the antigen-induced bronchoconstriction peaked at 6 min. SM-10661 inhibited the response with an ID50 of 45 mg/kg. Histamine- and leukotriene D4-induced bronchoconstrictions were unaffected by up to 100 mg/kg SM-10661. Ovalbumin challenge of minced lungs from passively sensitized guinea pigs triggered the release of leukotrienes and histamine. SM-10661 had no effect on the antigen-induced release of peptide leukotrienes or histamine up to 10(-4) M. These results indicate that SM-10661 may be a useful tool to investigate the role of PAF in antigen-induced anaphylactic bronchoconstriction.

Topics: Anaphylaxis; Animals; Asthma; Bronchoconstriction; Disease Models, Animal; Dose-Response Relationship, Drug; Guinea Pigs; Indomethacin; Male; Ovalbumin; Platelet Activating Factor; Propranolol; Pyrilamine; SRS-A; Thiazoles; Thiazolidines

The selective hetrazepinoic platelet-activating factor (PAF) antagonist WEB 2170 (Bepafant) was used to study the pathophysiological role of PAF in several models of anaphylaxis in mice and guinea pigs. In actively sensitized mice, the PAF antagonist WEB 2170 (1.0-10 mg/kg p.o.) protected mice from anaphylactic death in a dose-dependent manner when the anaphylactic response was potentiated by the beta-receptor antagonist propranolol. When active anaphylaxis in guinea pigs was induced intravenously by 100 mg/kg ovalbumin (OA) in the presence of small doses of the antihistamine mepyramine, additional treatment with oral or intravenous WEB 2170 protected the guinea pigs from anaphylactic death. Also, the remaining anaphylactic bronchoconstriction and blood pressure changes (including anaphylactic hypotension) were attenuated. When guinea pigs were passively sensitized with a heterologous antibody via the tracheal route and then challenged by ovalbumin (100 mg/kg i.v.) 24 hr after sensitization in the presence of 0.003 mg/kg i.v. mepyramine, additional treatment with tracheal WEB 2170 at 0.1-1 mg/kg protected the guinea pigs dose-dependently not only from anaphylactic death but also from a further decrease of respiratory flow and changes of blood pressure. Increased levels of PAF-like activity (20-50 ng PAF/whole lung) were detected in lungs removed from antigen-challenged animals. The results suggest a causative role for PAF in active and passive anaphylaxis.

Topics: Anaphylaxis; Animals; Azepines; Blood Pressure; Guinea Pigs; Lung; Male; Mice; Mice, Inbred Strains; Ovalbumin; Passive Cutaneous Anaphylaxis; Platelet Activating Factor; Propranolol; Pyrilamine; Respiration; Triazoles

1. It has been shown that opioid peptides modulate airway function. In the present study, the effect of beta-endorphin on antigen-induced contractions of isolated tracheal rings from actively sensitized guinea-pigs has been studied. 2. beta-Endorphin had a concentration-dependent bimodal effect on anaphylactic contractions of the trachea. Low concentrations of beta-endorphin (10(-10) and 10(-8) M) significantly potentiated anaphylactic contractions, whereas higher concentrations (10(-7) and 10(-6) M) significantly suppressed anaphylactic contractions of guinea-pig trachea. 3. beta-Endorphin in concentrations of 10(-8) M and 10(-7) M did not affect the responsiveness of the tracheal rings to histamine or leukotriene D4. This indicates that beta-endorphin does not influence the responsiveness of tracheal smooth muscle to anaphylactic mediators. 4. In the presence of the non-selective opioid receptor antagonist naloxone, 10(-8) M beta-endorphin still potentiated the anaphylactic contractions of the trachea. In addition, an equimolar concentration of des-Tyr1-beta-endorphin, a fragment of beta-endorphin without opioid-like activity, also potentiated anaphylactic contractions. The potentiation of anaphylactic contraction by 10(-8) M beta-endorphin is not therefore mediated by classical opioid-receptors. 5. In the presence of naloxone, 10(-7) M, beta-endorphin did not suppress anaphylactic contractions of the trachea. Thus, the suppression of anaphylactic contraction is mediated via a classical opioid-receptor. 6. In epithelium-denuded trachea, both 10(-8) and 10(-7) M beta-endorphin suppressed the anaphylactic contractions, whereas 10(-8) and 10(-7) M des-Tyr1-beta-endorphin did not affect anaphylactic contractions. It is concluded that the potentiation of the anaphylactic contraction in intact trachea is epithelium-dependent whereas the suppression of the anaphylactic contraction is epithelium-independent.

Topics: Anaphylaxis; Animals; beta-Endorphin; Epithelium; Guinea Pigs; Histamine; In Vitro Techniques; Male; Muscle Contraction; Muscle, Smooth; Naloxone; Ovalbumin; Peptide Fragments; SRS-A; Trachea

Twenty-four hours after an active anaphylactic shock induced by inhalation of antigen in conscious guinea pigs sensitized by a large dose of ovalbumin in complete Freund's adjuvant, a noteworthy bronchial inflammation, characterized by increased numbers of neutrophils, mononuclear cells and eosinophils in the bronchoalveolar lavage fluid, was observed. Some drugs administered after the anaphylactic shock were investigated using this model. Disodium cromoglycate primarily reduced the number of mononuclear cells and eosinophils. Dexamethasone and theophylline decreased the number of eosinophils. Salbutamol and mepyramine increased neutrophils. Indomethacin did not give rise to any significant effect. This test appears to be of use for the investigation of anti-inflammatory compounds in the prophylactic treatment of asthma.

Topics: Albuterol; Anaphylaxis; Animals; Asthma; Bronchitis; Bronchoalveolar Lavage Fluid; Cromolyn Sodium; Dexamethasone; Disease Models, Animal; Guinea Pigs; Male; Ovalbumin; Pyrilamine

1. Parameters of isolated hearts from rats which were actively sensitized to ovalbumin were found to be impaired on ovalbumin challenge: the heart rate increased whereas the contractility force and coronary flow decreased significantly. 2. Treatment in vivo or in vitro with histamine receptor antagonists (promethacine and cimetidine), the leukotriene antagonist FPL 55712, the PAF antagonist BN 52021, the combined prostaglandin endoperoxide receptor antagonist/thromboxane A2 synthesis inhibitor R 68070, the thromboxane synthetase inhibitor HOE 944, the lipoxygenase inhibitor ZIMET 47/79, the antioxidant sodium hyposulfite or with dexamethasone caused a different improvement of the parameters to a different degree. 3. Consequently, histamine, leukotrienes, PAF, activated oxygen, thomboxane A2 and possibly further autacoids might be involved in mediating the described anaphylactic reaction.

Topics: Adamantane; Anaphylaxis; Animals; Chromones; Coronary Circulation; Female; Heart; Heart Rate; Imidazoles; In Vitro Techniques; Myocardial Contraction; Myocardium; Naphthalenes; Ovalbumin; Pentanoic Acids; Pyridines; Rats

The aim of this study was to examine the ability of the novel PAF (platelet-activating factor) antagonist WEB 2170 to inhibit active anaphylaxis in mice and guinea pigs. Previous studies with other PAF antagonists have given equivocal results. This study was designed to define conditions under which a clear and significant effect of the PAF antagonist would be shown. WEB 2170 could be shown active, at concentrations of between 1 and 10 mg/kg p.o. in a model of murine anaphylaxis, in which the mice were actively sensitized and also treated with the beta-adrenoceptor antagonist propranolol to potentiate the anaphylactic response. WEB 2170 was also active in guinea pig models of anaphylaxis (tested dose range: 5 mg/kg i.v. and 0.04-3 mg/kg p.o.), in which the guinea pigs were sensitized according to one of three specified immunization schedules and pretreated with low doses of mepyramine before antigen challenge. These results suggest that PAF has a role in active anaphylaxis in mice and guinea pigs. However, to demonstrate this effect in guinea pigs, models must be used in which the effects of histamine release are minimized.

Topics: Anaphylaxis; Animals; Azepines; Blood Pressure; Bronchoconstriction; Guinea Pigs; Immunization; Male; Mice; Ovalbumin; Platelet Activating Factor; Propranolol; Pulmonary Ventilation; Pyrilamine; Triazoles

Animal models of allergic gastroenteropathy have defined both morphologic and physiologic changes that accompany the immune-mediated reaction to a dietary protein. In such models a broadening of the allergic response to other dietary proteins present in the gastrointestinal tract may occur during the localized anaphylactic reaction. The characteristic histologic intestinal findings of food protein-induced enteropathy may develop in selected infants with protracted diarrhea after infectious enteritis. Mechanisms underlying the induction of this response remain to be explained, but they may in part be similar to the broadening of the hypersensitivity response seen in experimental models of allergic enteropathy.

Topics: Acute Disease; Anaphylaxis; Animals; Gastroenteritis; Intestinal Mucosa; Mice; Milk Hypersensitivity; Ovalbumin; Stomach

Hyperreactivity and bronchial inflammation resulting from active anaphylactic shock induced by aerosol have been studied in guinea pigs after sensitization by intramuscular injection of large-dose ovalbumin or aerosol ovalbumin. When animals were sensitized by i.m. injection of 30 mg/kg ovalbumin, hyperreactivity to inhalation of histamine was obtained 1-3 h after shock. In bronchoalveolar lavage (BAL) fluid an increase in the number of eosinophils (6-48 h after shock) and neutrophils (6-24 h) was observed. When guinea pigs were sensitized by aerosol route, the hyperreactivity to histamine inhalation appeared 1-6 h after shock. In BAL fluid the number of mononuclear cells dropped (1-3 h) and then increased (24-48 h); the number of neutrophils (6-48 h) and eosinophils (24-48 h) increased. The results observed during these two types of sensitization were compared to those obtained after sensitization by injection of a large dose of ovalbumin mixed with Freund's complete adjuvant.

Topics: Aerosols; Anaphylaxis; Animals; Bronchitis; Bronchoalveolar Lavage Fluid; Eosinophils; Guinea Pigs; Hypersensitivity; Injections, Intramuscular; Male; Neutrophils; Ovalbumin

Previous studies have shown that an anaphylactic reaction in the isolated perfused heart is characterized by drastic coronary constriction, arrhythmias, and severe impairment of contractility. In vivo anaphylaxis is associated with myocardial ischemia and rapid cardiovascular failure. Recently, not only histamine but also platelet activating factor (PAF) has been implicated in cardiac manifestation of anaphylaxis. The present study was designed to separate the effects of PAF from those of histamine on cardiovascular function during systemic anaphylaxis. In guinea pigs, sensitization was produced by subcutaneous (s.c.) application of ovalbumin. Fourteen days after sensitization, the effects of an intravenous (i.v.) infusion of ovalbumin were tested in anesthetized artificially ventilated guinea pigs. The renewed application of the antigen induced severe cardiac dysfunction. Within 3 min, cardiac output (CO) had already decreased by 90% and left ventricular end-diastolic pressure (LVEDP) increased significantly, indicating left ventricular pump failure. Concurrently, ECG recordings uniformly showed signs of acute myocardial ischemia. In addition, arrhythmias occurred in terms of atrioventricular block. After 4 min, blood pressure (BP) rapidly decreased. All animals died within 10 min. Pretreatment with the H1-receptor antagonist mepyramine (1 mg/kg i.v.) in combination with the H2-receptor antagonist cimetidine (10 mg/kg i.v.) delayed onset of myocardial ischemia, arrhythmias and cardiac pump failure. After 10 min, however, LV contractility and BP steadily decreased, leading to severe hypotension within 30 min. If the selective PAF antagonist WEB 2086 (1 mg/kg i.v.) was administered in addition to cimetidine and mepyramine, myocardial ischemia and LV contractile failure were markedly inhibited further. In contrast, pretreatment with WEB 2086 alone had no beneficial effects on the anaphylactic cardiovascular changes. Therefore, we conclude that histamine is the predominant mediator during the early phase of systemic anaphylaxis whereas PAF-mediated effects are involved in cardiac dysfunction during the protracted late phase of anaphylaxis.

Topics: Anaphylaxis; Animals; Arrhythmias, Cardiac; Azepines; Blood Pressure; Cardiac Output; Cimetidine; Electrocardiography; Female; Guinea Pigs; Heart Rate; Hemodynamics; Histamine; Male; Myocardial Contraction; Ovalbumin; Platelet Activating Factor; Pyrilamine; Triazoles

Further evidence is reported on the influence exerted by capsaicin on the anaphylactic reaction evoked in actively sensitized guinea-pigs. In Herxheimer microshock induced by ovalbumin aerosol, pretreatment of animals with 100 micrograms/kg i.p. capsaicin prolonged the preconvulsion time when the drug was administered 3 h before antigen challenge. In contrast, the same dose of capsaicin injected 30 min before aerosol caused a shortening of latency of the respiratory symptomatology. The influence of the drug is no longer evident after 24 h. In "in vitro" experiments desensitization to capsaicin of tracheal preparations caused a reduction of histamine and SRS-A released during antigen challenge, in comparison to controls. Moreover, anaphylactic histamine release was increased in preparations perfused with 10(-8) M substance P. In conclusion, our findings confirm that neuropeptides may be involved in the pathogenesis of asthma by affecting release of mediators.

Topics: Anaphylaxis; Animals; Asthma; Capsaicin; Guinea Pigs; Histamine Release; Ileum; Male; Ovalbumin; Respiratory System; Trachea

The mechanisms underlying the different sensitivity to respiratory anaphylaxis were studied in two inbred strains of guinea pigs with high (IMM/S) or low (IMM/R) sensitivity to ovalbumin (OA) aerosol-induced respiratory anaphylaxis. Guinea pigs were immunized with OA in Freund's complete adjuvant and lymphocyte stimulation tests were done with cells from the tracheobroncheal lymph nodes (TBL) draining the airways, from peripheral blood lymphocytes and from the axillary and inguinal lymph nodes. The TBL of the IMM/R strain had a significantly lower response than those of the IMM/S strain. This selectively low response, which was not antigen specific, could be increased by cyclophosphamide pretreatment. The high TBL response in the IMM/S strain was decreased by OA inhalations to the level of the IMM/R strain. OA inhalations decreased the IgE response in the IMM/S but not the IMM/R strain. Different interpretations of these findings are discussed, with emphasis on the possibility that an inherent suppressor cell population in the TBL are involved.

Topics: Anaphylaxis; Animals; Asthma; Bronchi; Bronchial Provocation Tests; Cyclophosphamide; Guinea Pigs; Hypersensitivity; Immunoglobulin E; Inbreeding; Lymph Nodes; Lymphocyte Activation; Lymphocytes; Ovalbumin; Trachea

As ozone (O3) is known to cause airway inflammation and hyperresponsiveness, we examined the effects of O3 exposure (1, 3, or 5 ppm, 2 h) on sensitization and provocation in guinea pigs sensitized with ovalbumin (OA) through the airway. In groups exposed to O3 before sensitization, 5 ppm increased the production of IgG1 antibodies and decreased the OA sensitization threshold from 0.01 to 0.002%. In those exposed before provocation, 1, 3, or 5 ppm of O3 decreased the OA provocation threshold from 0.5 to 0.02%, and this enhancement appeared to depend on airway hyperresponsiveness. We conclude that O3 exposure may play an important role in causing asthmatic attacks rather than enhancing allergic sensitization.

Topics: Anaphylaxis; Animals; Asthma; Female; Guinea Pigs; Immunization, Passive; Immunoglobulin G; Ovalbumin; Ozone

The capacity of the stomach to participate in anaphylaxis induced by the hapten N,N'-di-2,4,dinitrophenyllysine (di-DNP-lysine) was examined in BDF1 female mice immunized with dinitrophenylated Ascaris suum extract. Immunized animals underwent laparotomy and nontraumatic pyloric occlusion using a microvascular clamp. Following wound closure, animals were gavage-fed ovalbumin together with di-DNP-lysine. Other mice were subjected to systemic anaphylaxis by intravenous injection of di-DNP-lysine administered 1 min after gavage feeding of ovalbumin. The intravenous and intragastric administration of di-DNP-lysine led to a sixfold or greater increase in serum immunoreactive ovalbumin. Examination of 1-micron sections of gastric tissue from DNP-Asc-immunized and unimmunized mice showed an intact mucosal and submucosal architecture. A 75% increase in the number of mast cells below the muscularis mucosa was seen in immunized compared with unimmunized BDF1 mice. Gastric tissue sections from immunized mice challenged orally or intravenously with di-DNP-lysine showed compaction of erythrocytes in blood vessels, degranulation of mast cells, degenerative changes in the gastric epithelium, expulsion of mucus from gastric glands, and edema in the lamina propria. The present model may be useful for further defining the consequences of anaphylaxis on the development of immune responses to dietary antigens.

Topics: Anaphylaxis; Animals; Capillary Permeability; Cell Count; Cell Membrane Permeability; Female; Gastric Mucosa; Haptens; Immunization; Lysine; Mast Cells; Mice; Ovalbumin

Eosinophil infiltration into bronchoalveolar areas of the lung has been assessed in guinea pigs sensitized to ovalbumin (OA) and then challenged with the aerosolized antigen. Cell content, histamine, and guinea pig albumin (GPA) have been measured in bronchoalveolar lavage (BAL) fluid from these animals. Extensive eosinophil accumulation resulted from sensitization followed by OA challenge; monocytes that initially accounted for greater than 80% of the BAL cells remained essentially constant, and neutrophils comprised less than 3% of the population throughout. Eosinophils were elevated at 3 h, peaked with a fivefold increase at 24 h, and remained elevated for at least 7 days. Histopathologic changes observed in lungs taken from sensitized guinea pigs 24 h after OA challenge confirm this eosinophilia. Increased histamine and GPA were detected only at 5 min. Oral treatment with betamethasone (ED50 = 0.4 mg/kg), phenidone (ED50 = 15 mg/kg), Sch 37224 (ED50 = 0.5 mg/kg), and WEB 2086 (ED50 = 4 mg/kg) decreased eosinophil accumulation in the BAL fluid, indicating roles for 5-lipoxygenase products and PAF in this multimediator-dependent model of allergic inflammation. On the other hand, 4 mg/kg of indomethacin increased total cells with no effect on eosinophils, precluding a major role for cyclooxygenase products. Sch 37224, an antileukotriene agent and an orally active novel antiallergy agent in sheep, guinea pigs, and humans, is as potent as betamethasone at blocking eosinophil infiltration, suggesting that it may also suppress human pulmonary inflammation.

Topics: Albumins; Anaphylaxis; Animals; Asthma; Azepines; Betamethasone; Bronchoalveolar Lavage Fluid; Cell Count; Eosinophils; Guinea Pigs; Histamine; Immunization; Indomethacin; Leukotriene Antagonists; Lipoxygenase Inhibitors; Lung; Male; Naphthyridines; Ovalbumin; Platelet Activating Factor; Pyrazoles; Thromboxanes; Triazoles

It has been shown that opioid peptides induce histamine release and enhance antigen-induced histamine release from isolated peritoneal mast cells. Little is known about the effect of opioid peptides on mast cells present in airway smooth muscle. In the present study, the effect of beta-endorphin on antigen-induced contractions of isolated tracheal rings from actively sensitized guinea pigs was studied. It appears that beta-endorphin has a bidirectional effect on anaphylactic contractions of the trachea. Low concentrations of beta-endorphin (0.1 and 10 nM) significantly potentiate the anaphylactic contractions of tracheal rings. In contrast, higher concentrations of beta-endorphin (0.1 and 1 microM) significantly suppress the anaphylactic contractions of guinea pig trachea. In the presence of the non-selective opioid receptor antagonist naloxone, 10 nM of beta-endorphin still potentiates the anaphylactic contractions of the trachea. This demonstrates that the potentiation of anaphylactic contractions of guinea pig trachea by low concentrations of beta-endorphin is not mediated by opioid receptors. We speculate that the potentiation of the anaphylactic contraction by beta-endorphin is due to an interaction with mast cells.

Topics: Anaphylaxis; Animals; beta-Endorphin; Guinea Pigs; In Vitro Techniques; Male; Mast Cells; Muscle Contraction; Muscle, Smooth; Naloxone; Ovalbumin; Trachea

The effect of chronic dietary antigen challenge on the intestine was examined in sensitized rats. Three groups of Hooded-Lister rats were studied: animals sensitized to egg albumin; sham-sensitized animals; and unmanipulated controls. In sensitized rats, serum immunoglobulin E titers to egg albumin were greater than or equal to 1:64, whereas control and pair-fed rats showed no response. Sensitized rats received egg albumin 1 mg/ml in drinking water and rat chow ad libitum. Pair-fed animals also received egg albumin but were pair-fed with sensitized animals. Controls received water and rat chow ad libitum. Chronic antigen challenge resulted in reduced food intake and weight gain in sensitized animals. When the rats were killed after 9 days of antigen exposure, proximal intestine from experimental animals showed decreased disaccharidase activity, brush-border microvillus surface, area, and villus height. Crypt depth and enterocyte migration rate were increased. Mucosal mast cell involvement was suggested by mast cell proliferation, evidence of mast cell degranulation, and increased serum rat mast cell protease II levels. At the time of death, only sensitized jejunum demonstrated an increase in short-circuit current in Ussing chambers in response to antigen challenge. The findings indicate that chronic antigen exposure leads to intestinal injury, reduced food intake, and diminished weight gain.

Topics: Anaphylaxis; Animals; Antigens; Body Weight; Female; Food Hypersensitivity; Immunization; Immunoglobulin E; Intestinal Diseases; Intestinal Mucosa; Intestine, Small; Mast Cells; Microscopy, Electron; Ovalbumin; Peptide Hydrolases; Rats; Rats, Inbred Strains

An anaphylactic reaction in the isolated perfused heart is characterized by a drastic coronary constriction, arrhythmias, and an impairment of contractility. In vivo anaphylaxis is associated with respiratory distress and cardiovascular failure. The present investigation was designed to ascertain the electrocardiographic and cardiovascular changes during systemic hypersensitivity reactions. In addition, an attempt was made to differentiate cardiac from respiratory events. In guinea pigs, sensitization was produced by s.c. administration of ovalbumin together with Freund's adjuvant solution. Fourteen days after sensitization, the effects of an i.v. infusion of ovalbumin were tested in the anesthetized guinea pigs, which were ventilated with room air or 100% oxygen. A second administration of the antigen induced the development of cardiovascular collapse, leading to death within 12 min. Within 3 min, cardiac output decreased by 90% and end-diastolic left ventricular pressure increased significantly, indicating left ventricular pump failure. In the same time range, ECG recordings uniformly showed signs of acute myocardial ischemia. In addition, arrhythmias occurred in the form of atrioventricular block. Left ventricular contractility declined continuously within the first 4 min. Finally, after 4 min, blood pressure steadily decreased. During ventilation with room air, severe hypoxia developed, with arterial PO2 decreasing from 94 mmHg to 14 mmHg after 3 min. However, under ventilation with 100% oxygen, a dissociation between cardiac damage and respiratory distress occurred. Myocardial ischemia and signs of cardiac failure preceded the development of hypoxia by a significant time interval. It is to be concluded that cardiac damage is a primary event in anaphylactic shock. Furthermore, the electrocardiographic signs of ischemia are interpreted as a result of coronary artery spasm.

Topics: Anaphylaxis; Animals; Arrhythmias, Cardiac; Blood Gas Analysis; Blood Pressure; Cardiac Output; Coronary Disease; Electrocardiography; Female; Freund's Adjuvant; Guinea Pigs; Heart; Heart Ventricles; Hypoxia; Immunization; Male; Ovalbumin; Respiration

Antigenicity studies of mofezolac (N-22) were examined in mice and guinea pigs and the following results were obtained. The findings of active systemic anaphylaxis, passive hemagglutination test, 4 hour passive cutaneous anaphylaxis (4-hr PCA) and 8-day PCA in guinea pigs revealed that N-22 possessed neither immunogenic nor eliciting potentiality. However, N-22 was shown to be eliciting antigenicity in mice when given N-22-ovalbumin conjugate plus Freund's complete adjuvant (FCA) as immunogen.

Topics: Anaphylaxis; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antigens; Female; Freund's Adjuvant; Guinea Pigs; Hemagglutination Tests; Isoxazoles; Male; Mice; Mice, Inbred BALB C; Ovalbumin; Passive Cutaneous Anaphylaxis; Rats; Rats, Inbred Strains

Topics: Anaphylaxis; Animals; Body Temperature; Cerebral Ventricles; Enkephalin, Methionine; Injections, Intraventricular; Male; Ovalbumin; Rats; Rats, Inbred Strains

Topics: Acoustic Stimulation; Acute Disease; Anaphylaxis; Animals; Body Temperature; Chronic Disease; Electroshock; Hematocrit; Ovalbumin; Rats; Stress, Psychological

Topics: Anaphylaxis; Animals; Brain Diseases; Cerebral Ventricles; Female; Injections, Intraventricular; Ovalbumin; Rats; Rats, Inbred Strains

Groups of rats previously sensitized systemically on day 0 with a low dose of ovalbumin (OVA) were gavaged daily with ovalbumin or bovine serum albumin or a mixture of both proteins from day 14 to 18. Blood samples were obtained pre- and post-challenge and serum levels of the rat mast cell protease II (RMCPII) determined by immunoassay. Release of this specific mucosal mast cell mediator was only observed in animals challenged with ovalbumin and the initial challenge released levels of RMCPII 15-fold higher than normal resting levels (P less than 0.001). Subsequent daily challenges evoked the release of significantly lower levels of mediator (P less than 0.001 relative to day 14), but with one exception each test group released significantly more RMCPII than the matched control group on each day (P less than 0.001-P = 0.015). An increased uptake of BSA 'bystander' protein was observed when OVA-sensitized animals were repeatedly gavage-challenged with OVA but there was no correlation with the release of RMCPII mediator. After a 9-day rest period the levels of RMCPII released 6 hr post-challenge on day 26 were still significantly lower (P = 0.004) than the levels of mediator released on day 14. In contrast, animals not previously challenged were still capable of releasing high levels of mediator at the time of first mucosal contact. The levels of RMCPII detected in the serum after enteral protein antigen challenge never exceeded 6000 ng/ml and were lower than those previously observed in parasitized rats following intravenous antigen challenge.

Topics: Anaphylaxis; Animals; Antigens; Chymases; Disease Models, Animal; Food Hypersensitivity; Immunization; Injections, Intraperitoneal; Intestinal Mucosa; Intubation, Gastrointestinal; Mast Cells; Ovalbumin; Rats; Rats, Inbred Strains; Serine Endopeptidases

Buspirone hydrochloride(buspirone) and buspirone-ovalbumin mixture were examined for their antigenicity in guinea pigs and mice in comparison with ovalbumin (OVA) and 2, 4-dinitrochlorobenzene (DNCB)-OVA conjugate. The results obtained were as follows: 1. When guinea pigs were sensitized with buspirone or buspirone-OVA emulsified with Freund's complete adjuvant (FCA), these animals showed negative reactions in active systemic anaphylaxis (ASA), active cutaneous anaphylaxis (ACA), passive cutaneous anaphylaxis (PCA), passive hemagglutination (PHA) and Schultz-Dale test. 2. When mice were sensitized with buspirone or buspirone-OVA adsorbed to alum, these animals revealed a negative reaction in PCA using rats. 3. As positive controls, guinea pigs were sensitized with OVA or DNCB-OVA emulsified with FCA, and mice with OVA or DNCB-OVA adsorbed to alum. As a result, these animals disclosed positive reactions in ASA, ACA, PCA, PHA and Schultz-Dale test. As shown above, buspirone was considered to possess neither antigenic nor haptenic properties.

Topics: Anaphylaxis; Animals; Antigens; Buspirone; Dinitrochlorobenzene; Guinea Pigs; Hemagglutination; Intradermal Tests; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Ovalbumin; Passive Cutaneous Anaphylaxis

1. Serum IgG levels of sensitized guinea-pigs bled at various times after the booster injection were evaluated and its capacity to sensitize passively lung strips from normal guinea-pigs assessed. Following the booster injection, both serum IgG and the ability to sensitize passively lung strips increased during the first week and decreased slowly thereafter. 2. The PAF antagonist WEB 2086 (3 mg kg-1, i.v.) blocked the anaphylactic bronchoconstriction induced by intravenous administration of ovalbumin (1 mg kg-1) when guinea-pigs were challenged 2 and 4 days after the booster injection, but became ineffective when tested in guinea-pigs challenged 7, 28 and 56 days after the booster injection. 3. The ability of WEB 2086 to reduce anaphylactic bronchoconstriction of guinea-pigs challenged 2 and 4 days after the booster injection was unrelated to either the selective involvement of one type of immunoglobulin, low IgG titres in sera or a reduced sensitizing capacity. 4. The booster injection, which accounts for the loss of efficacy of WEB 2086 from the fourth day thereafter, probably operates as a PAF-independent inflammatory challenge. 5. The protocol for immunisation and the day of experiment after the booster injection determines the sensitivity of the anaphylactic bronchoconstriction to inhibition of PAF antagonists.

Topics: Anaphylaxis; Animals; Azepines; Blood Cell Count; Bronchi; Enzyme-Linked Immunosorbent Assay; Guinea Pigs; Histamine; Immunization, Secondary; Immunoglobulin G; Lung; Ovalbumin; Platelet Activating Factor; Radioimmunoassay; Spectrometry, Fluorescence; Thromboxane B2; Triazoles

Since several studies indicate that protection from lethal anaphylaxis is mediated by anterior hypothalamic (AH) lesions, we investigated the hypothesis that central nervous system perturbations can modify release of mediators from antigen-challenged sensitized lungs. Three types of perturbations were made in guinea pigs: AH perturbation (electrodes inserted and the current was applied), anterior hypothalamic sham (AS) (electrodes placed as in the AH group but no current was passed), and posterior hypothalamic (PH) perturbation (electrodes placed and the current was applied). A control group was sham operated (electrodes not inserted). Eleven days after the operation, guinea pigs receiving brain perturbations and half the control group were sensitized to the antigen ovalbumin. The other half of the control group received vehicle only (nonsensitized). Twenty-five days after this procedure, lungs were perfused in situ, and the outflows were collected before and after injection of antigen. The perfusates were assayed for immunoreactive prostaglandin and histamine, and the lungs were assayed for cAMP, guanosine monophosphate, and histamine. Release of mediators and changes in lung cyclic nucleotides after perfusion with antigen were significantly greater in all the antigen-sensitized compared to the nonsensitized animals. Within the anaphylactic groups, significant reductions in mediators and in cyclic nucleotides were found in the animals with perturbations of the AH region compared to the CO animals. The time course of mediator release was not altered. The results extend to the biochemical level, the observation that the perturbation of the AH region can markedly modify the anaphylactic response, and indicate that this effect may be due to altered release of mediators.

Topics: Anaphylaxis; Animals; Arachidonic Acid; Arachidonic Acids; Brain; Guinea Pigs; Histamine Release; Hypothalamus, Anterior; Hypothalamus, Posterior; Lung; Male; Organ Size; Ovalbumin; Stereotaxic Techniques

The influence of capsaicin on anaphylactic reactions in the guinea-pig was studied both in vivo and in vitro. In guinea-pigs actively sensitized with ovalbumin, Herxheimer microshock was elicited by antigen aerosol and the preconvulsion time recorded. The preconvulsion time was reduced by about 30% in animals pretreated with capsaicin (1 mg/kg) injected i.p. 30 min before antigen aerosol, whereas it remained unchanged when the drug was administered two days before aerosol treatment. Capsaicin shows a partial protective effect when the provocative aerosol was administered 3 h after the last of three doses of capsaicin (100 micrograms/kg, i.p.), which had been injected for three consecutive days. Ileum longitudinal muscle strips were used for in vitro anaphylaxis studies. These were isolated from guinea-pigs actively sensitized with ovalbumin and histamine release evoked by antigen was measured. Preparations perfused with capsaicin (10(-6)-10(-4) M) and desensitized to the drug, showed a lower anaphylactic release of histamine. This effect was dose-dependent, with the histamine release reduced by 35% at higher concentrations (10(-5)-10(-4) M) of capsaicin. The mechanism of the influence of capsaicin on anaphylactic reactions is discussed briefly.

Topics: Anaphylaxis; Animals; Asthma; Capsaicin; Guinea Pigs; Histamine Release; In Vitro Techniques; Male; Muscles; Ovalbumin

Antigen challenge of jejunal epithelium from rats sensitized to egg albumin induces an active Cl- secretory process secondary to release of mucosal mast cell mediators. The present study was designed to define the relative role of these mast cell mediators and the enteric nervous system in the transport abnormalities associated with intestinal anaphylaxis. Net ion transport of stripped jejunal tissue from sensitized and sham-treated animals was studied in Ussing chambers. The Cl- secretory response induced by egg albumin during intestinal anaphylaxis was similar to that after addition of 5-hydroxytryptamine (5-HT), histamine, and prostaglandins D2 and E2 to jejunal tissue. Cinanserin, a 5-HT2-receptor antagonist, virtually abolished the response to 5-HT and totally abolished the response to egg albumin. Methysergide, a 5-HT1-receptor antagonist had no effect on either response. Indomethacin, an inhibitor of prostaglandin synthesis, significantly inhibited the 5-HT and egg albumin response. Diphenhydramine, an H1-receptor antagonist and cimetidine, an H2-receptor antagonist both significantly inhibited the histamine response but neither altered the response to egg albumin. Atropine, an anticholinergic, and tetrodotoxin, a nerve blocker, did not inhibit the antigen induced anaphylactic response. These results indicate that 5-HT, acting through 5-HT2 receptors is largely responsible for the transport abnormalities seen in intestinal anaphylaxis induced by egg albumin while prostaglandins appear to play a partial role. The findings do not support a role for the enteric nervous system for the egg albumin induced changes in Cl- secretion.

Topics: Anaphylaxis; Animals; Biological Transport; Cyclooxygenase Inhibitors; Electric Stimulation; Female; Histamine; Histamine Antagonists; Intestinal Diseases; Intestines; Ions; Mast Cells; Ovalbumin; Prostaglandins; Rats; Serotonin; Serotonin Antagonists; Tetrodotoxin

We examined the mucosal barrier function during anaphylaxis induced by the hapten N,N'-di-2,4,dinitrophenyl-lysine (di-DNP-lysine) in BDF1 female mice immunized with dinitrophenylated Ascaris suum extract. Immunized mice were gavaged with 10 mg or 50 mg of ovalbumin (OVA) with or without N,N'-di-2,4,-DNP-lysine (di-DNP-lysine). Animals that received di-DNP-lysine underwent anaphylaxis and were observed to have significantly greater serum concentrations of immunoreactive OVA (iOVA) than control mice. The severity of anaphylaxis, which varied with the dose of di-DNP-lysine administered, influenced the uptake of OVA; greater amounts of iOVA were detected in serum of mice undergoing more severe anaphylaxis. On gel permeation of serum from both groups of mice, immunoreactive OVA was found to have a molecular size similar to native OVA. Di-DNP-lysine is a synthetic hapten that reliably induced anaphylaxis in sensitized animals challenged by gavage. Anaphylaxis resulted in the uptake into the circulation of greater quantities of an unrelated protein antigen present in the intestinal lumen. The protein antigen that was taken up into the circulation appeared to be intact and thus may have an influence on the development of the immune response, or lack thereof, to this bystander antigen.

Topics: Anaphylaxis; Animals; Intestinal Absorption; Intestinal Diseases; Lysine; Mice; Ovalbumin; Permeability

Neutrophils are prominent in some IgE-mediated allergic reactions and may contribute to the pathophysiology of immediate hypersensitivity. Antigen challenge of fragments of guinea pig lung tissue that were passively sensitized with IgE or IgG antibody evoked the release of neutrophil chemotactic activity (NCA) in parallel with histamine. The NCA released from lung tissue by both IgG- and IgE-dependent stimulation coeluted from a column of Sephacryl S-300 with synthetic leukotriene B4 (LTB4). The NCA in eluates from the Sephacryl S-300 column contained LTB4, as determined by high-performance liquid chromatography and specific radioimmunoassay, in quantities that accounted for the observed chemoattractant activity in the eluates. Furthermore, the NCA of supernatants from antigen-challenged lung fragments was reduced by a mean of 80% after absorption with a monoclonal antibody to LTB4. LTB4 thus constitutes the major functional constituent of NCA released after anaphylactic challenge of IgE- and IgG-sensitized guinea pig lung tissue.

Topics: Anaphylaxis; Animals; Chemotactic Factors; Guinea Pigs; Immunization, Passive; Immunoglobulin E; Immunoglobulin G; Interleukin-8; Leukotriene B4; Lung; Male; Neutrophils; Ovalbumin

The effects of nedrocromil sodium and disodium cromoglycate were studied on the anaphylactic contraction of guinea-pig trachea in two models of active sensitization (IgE and IgG models). The influence of epithelial removal on the effects of nedocromil sodium and disodium cromoglycate was examined because several studies have shown that the epithelial layer can modulate agonist- or antigen-induced contractile responses. Disodium cromoglycate (10(-4) M) and nedocromil sodium (10(-4) M) provided significant protection against antigen-induced contractions of guinea-pig tracheal smooth muscle in the IgG model. But only nedocromil sodium had an effect at this concentration in the IgG model and was also effective at 10(-5) M in the epithelium-denuded tracheal strips. At this concentration, disodium cromoglycate lost its protective effect. Comparison with the results obtained with FPL-55712, AA-861 and mepyramine suggested that these drugs affect histamine and particularly leukotriene synthesis and/or release by mast cells or other immunocompetent cells. These findings indicate that nedocromil sodium inhibits the IgE- and IgG-related antigen-induced contraction in guinea-pig airways, whereas disodium cromoglycate inhibits only the IgG-related processes. This study supports the hypothesis that these drugs modulate antigen-induced mediator synthesis and/or release from immunocompetent cells.

Topics: Airway Resistance; Anaphylaxis; Animals; Benzoquinones; Chromones; Cromolyn Sodium; Flavonols; Guinea Pigs; Immunoglobulin E; Immunoglobulin G; In Vitro Techniques; Male; Nedocromil; Ovalbumin; Pyrilamine; Quercetin; Quinolones; Quinones; Trachea

Leukotriene C4 (LTC4) underwent rapid elimination from the circulating blood and was extensively converted to LTD4 within the vascular space of the guinea pig. To mimic the elimination and metabolism of endogenous LTC4 generated during anaphylaxis, 14,15-3H-labeled LTC4 was infused intravenously over a period of 15 min, leading to a recovery in bile of 85% of the infused LT radioactivity within 2 h. Corresponding to the tracer studies, LTD4 and, to a lesser extent, LTC4 were the predominant endogenous cysteinyl LTs in guinea pig bile. The biliary production rate of endogenous LTD4 increased from 0.3 +/- 0.1 to 6.2 +/- 1.8 pmol x min-1 x kg-1 (p less than 0.001) during anaphylactic shock induced by intravenous injection of OVA (0.2 mg/kg) into sensitized guinea pigs. A novel LT biosynthesis inhibitor (MK-886; 10 mg/kg, i.v., 15 min before antigen challenge) suppressed the antigen-induced cysteinyl LT production by greater than 92% (p less than 0.001). This inhibition of systemic LTC4 formation was associated with a complete protection against lethal anaphylactic shock in animals pretreated in addition with the H1 receptor antagonist pyrilamine. Pretreatment with either the inhibitor of LT synthesis or the histamine receptor antagonist reduced the lethality during anaphylactic shock from 100 to 60 and 78%, respectively. In artificially ventilated, pyrilamine-pretreated animals, the antigen-induced decrease in dynamic lung compliance and the rise in hematocrit were significantly reduced (p less than 0.05) by pretreatment with the inhibitor of LT synthesis. Dexamethasone at high doses (10 mg/kg, i.p., once daily for 7 d, or in a single dose of 10 mg/kg, i.v., 3.5 h before challenge) had no inhibitory effect on LT generation during anaphylaxis in vivo. However, in resident peritoneal macrophages, harvested from these dexamethasone-treated sensitized guinea pigs and stimulated with zymosan, both cysteinyl LT and 6-keto-PGF1 alpha formation were strongly suppressed. These studies indicate an important role of cysteinyl LTs in systemic anaphylaxis in vivo and demonstrate the blockade of anaphylactic LT generation by a novel inhibitor of LT biosynthesis (MK-886) but not by dexamethasone.

Topics: Anaphylaxis; Animals; Dexamethasone; Guinea Pigs; Hemodynamics; Indoles; Leukotriene Antagonists; Male; Ovalbumin; Respiration; SRS-A

The effect of disodium 4-chloro-2,2-iminodibenzoate (CCA) on IgE antibody response was examined in C3H/A and (BALB/c x C57BL/6J) F1 hybrid mice immunized with low doses of ovalbumin (OA) adsorbed on aluminium hydroxide gel. CCA administered orally at the doses of 5 and 50 mg/kg/day reduced IgE antibody production in these mice as determined by PCA test. High doses of CCA (100 mg/kg/day) given from day 7 before immunization of C57BL mice and during 1 week after immunization of mice with OA and Bordetella Pertussis Vaccine reduced the mortality of these mice subjected to anaphylactic shock on day 7 of immunization. CCA treatment was ineffective in anaphylactic shock of C57BL mice immunized with very high dose of OA, known to elicit little or no IgE antibody production but high IgG antibody response. The treatment of OA-immunized Guinea pigs with one oral dose of CCA (100 mg/kg) did not reduce mortality in protracted anaphylactic shock. Our results demonstrate that CCA inhibits IgE production as well as IgE mediated hypersensitivity reactions in mice.

Topics: Anaphylaxis; Animals; Antigens; Female; Guinea Pigs; Immunization; Immunoglobulin E; Immunoglobulin G; Immunosuppressive Agents; Male; Mice; Mice, Inbred C3H; ortho-Aminobenzoates; Ovalbumin

The generation of leukotrienes C4, D4 and E4 from arachidonic acid is dependent upon the activity of 5-lipoxygenase (5-LOX). The effects of RG 6866 (N-methyl-4-benzyloxyphenylacetohydroxamic acid) on the activity of guinea pig 5-LOX in vitro and in vivo were determined in the present study. The generation of 5-hydroxy-6,8,11,14-eicosatetraenoic acid (5-HETE) from arachidonic acid by isolated guinea pig peritoneal polymorphonuclear (PMN) cells was inhibited by incubation with RG 6866 (IC50 = 0.20 microM). A similar effect (IC50 = 0.23 microM) was observed when 5-HETE production was measured in a supernatant fraction from PMNs. Additionally, the compound did not inhibit 3H-LTD4 binding to guinea pig membranes. In actively sensitized guinea pigs pretreated with indomethacin, propranolol and pyrilamine, RG 6866 inhibited antigen-induced systemic anaphylaxis and LTD4-dependent bronchoconstriction in a dose-dependent manner following oral administration. In the pulmonary anaphylaxis model, significant (p less than 0.05) inhibition of the mortality was observed within 30 min and maintained through four hours after treatment with RG 6866 (50 mg/kg i.g.). Finally, orally administered RG 6866 inhibited the formation of LTC4 in these animals with an ED50 = 24.0 mg/kg. These findings indicate that RG 6866 is an inhibitor of 5-LOX both in vitro and in vivo.

Topics: Airway Resistance; Anaphylaxis; Animals; Arachidonate Lipoxygenases; Benzyl Compounds; Guinea Pigs; Hydroxamic Acids; In Vitro Techniques; Lipoxygenase Inhibitors; Male; Neutrophils; Ovalbumin; SRS-A

Topics: Anaphylaxis; Animals; Antigens; Azepines; Disease Models, Animal; Endotoxins; Escherichia coli; Guinea Pigs; Lung Diseases; Ovalbumin; Platelet Activating Factor; Pyrilamine; Shock, Septic; Triazines; Triazoles

The effect of glucocorticosteroid (GCS) treatment on ovalbumine-induced IgE-mediated immediate and late allergic response was studied in sensitized guinea pigs. The results show that the GCS budesonide (BUD) inhibits the allergen-induced IgE-mediated immediate and late bronchial obstruction. The effect on the early reaction is correlated to the inhibition of leukotrienes and histamine release. The importance of mediator release inhibition for the antianaphylactic effect of GCS is discussed. In examining the effect on the late reaction, it was found that BUD had to be present during the early reaction but did not inhibit the early reaction. Furthermore, the effect on the late reaction was correlated to the inhibition of vascular leakage but not to the infiltration of inflammatory cells as examined in bronchoalveolar lavage. The results indicate that some triggering factors important for the development of the late reaction are released during the early reaction. Inhibition of the release of that factor or the activation of inflammatory cells by that factor might be the mechanism behind the antiinflammatory activities of GCS.

Topics: Anaphylaxis; Animals; Antigens; Bronchi; Bronchial Provocation Tests; Budesonide; Cromolyn Sodium; Dimercaprol; Guinea Pigs; Histamine Release; Hypersensitivity; Hypersensitivity, Delayed; Immunoglobulin E; Leukotriene B4; Lung; Ovalbumin; Peptide Hydrolases; Pregnenediones; SRS-A

An anaphylactic reaction was induced with the specific antigen (1 mg Ovalbumin) in perfused lungs from actively sensitized guinea-pigs in order to evaluate the ability of the ginkgolide BN-52021 (0.4, 4, 40 micrograms/ml) to modulate the mediator release. The ginkgolide reduces in a dose dependent manner the release of histamine (22%, 45% and 75% of inhibition), TXB2 (77% of inhibition at the maximal dose used) and of SRS-A to a lower extent (only 33% at the higher dose). BN-52021 was still powerful in reducing histamine release induced by immunological reaction in indomethacin treated animals. In conclusion, the present "in-vitro" results confirm the beneficial activity of this ginkgolide, already demonstrated by the same Authors in "in-vivo" experiment, in anaphylactic reactions, and further substantiate the wider spectrum of action of the ginkgolide beside its specific PAF receptor antagonistic activity.

Topics: Anaphylaxis; Animals; Diterpenes; Ginkgolides; Guinea Pigs; Histamine; Histamine Release; Kinetics; Lactones; Lung; Male; Ovalbumin; SRS-A; Thromboxane A2; Thromboxane B2; Thromboxanes

Permeability changes in the guinea-pig skin following intradermal (i.d.) injection of tachykinin agonists or antigen were monitored through the extravasation of 99mTc-labelled human serum albumin and blood flow changes through the accumulation of 51Cr-labelled microspheres. A variety of synthetic and natural tachykinins, including substance P and neurokinins A and B, were shown to be potent inducers of permeability changes. Neurokinins A and B, but not substance P, were also shown to be apparent vasoconstrictor agents. Permeability responses in sensitized guinea pigs to i.d. injection of antigen and substance P, but not histamine, were abolished by pretreatment with the tachykinin antagonists [D-Arg1, D-Pro2, D-Trp7,9, Leu11]-substance P and [D-Pro2, D-Trp7,9]-substance P. Interpretation of such results was complicated by the fact that such antagonists may in themselves induce mast cell activation. Depletion of substance P containing neurons by pretreatment of guinea pigs with capsaicin also produced significant inhibition of antigen-induced permeability changes. These results indicate a possible role for tachykinins, such as substance P, in cutaneous anaphylaxis in the guinea pig.

Topics: Anaphylaxis; Animals; Capsaicin; Guinea Pigs; Injections, Intradermal; Male; Ovalbumin; Permeability; Receptors, Neurotransmitter; Receptors, Tachykinin; Skin; Substance P; Tachykinins

Inbred hyper-reactive rats, actively sensitized to OVA, were anesthetized, cannulated, and ventilated with room air. Tracheal instillation of Ag (OVA) resulted in an elevation of airways pressure (14.4 +/- 0.6 cm H2O). Measurement of biliary peptide leukotriene levels before and after Ag challenge using reverse phase HPLC and RIA techniques showed significant elevations in leukotriene (LT) levels, the amounts released being LTC4 (3.65 +/- 0.78), LTD4 (2.8 +/- 1.11), and N-Ac LTE4 (3.87 +/- 1.15) expressed as ng/100 g of body weight, n = 13. Identification of these metabolites were confirmed by HPLC/RIA techniques and LTC4 was further characterized by UV spectroscopy and its enzymatic conversion by gamma-glutamyl transpeptidase to LTD4. [3H]LTC4 (16 ng) administration by tracheal instillation resulted in a 31.4 +/- 4.3% recovery of radioactivity through the bile over 4 h (n = 3) with the major identified metabolite being N-Ac LTE4. [3H]LTC4 (16 ng) plus synthetic LTC4 (5 micrograms) showed a 30.8 +/- 3.1% recovery through the bile after tracheal instillation (3-h collection, n = 4) with significant amounts of LTC4 as well as N-Ac LTE4 present. [3H]LTC4 administration by the portal vein resulted in a 37.4 +/- 8.8% biliary recovery over 60 min (n = 6), the metabolites present in the bile being LTC4, LTD4, LTE4, and N-Ac LTE4. Pretreatment with the 5-lipoxygenase inhibitor L-656,224 (15 mg/kg, 3.5 h pre-p.o.) before Ag challenge resulted in a significant inhibition (greater than 90%, p less than 0.05) of biliary leukotriene levels in this model. Our study demonstrates that peptide leukotrienes are produced in the anesthetized rat after pulmonary anaphylaxis and that biliary leukotriene measurement is suitable for showing the biochemical efficacy of leukotriene inhibitors in vivo. In vivo tracer experiments suggest that the biliary metabolic profile of the peptide leukotrienes is dependent on the site and levels of release as well as the efficiency of the vascular clearance of the various metabolites.

Topics: Anaphylaxis; Animals; Bile; Leukotriene E4; Leukotrienes; Male; Ovalbumin; Peptide Biosynthesis; Rats; Rats, Inbred Strains; Respiratory Hypersensitivity; Sodium Chloride; SRS-A

Pertussis toxin is produced by the causative agent of whooping cough, Bordetella pertussis, and is an adenosine diphosphate (ADP)-ribosyltransferase capable of covalently modifying and thereby inactivating many eukaryotic G proteins involved in cellular metabolism. The toxin is a principal determinant of virulence in whooping cough and is a primary candidate for an acellular pertussis vaccine, yet it is unclear whether the ADP-ribosyltransferase activity is required for both pathogenic and immunoprotective activities. A B. pertussis strain that produced an assembled pertussis holotoxin with only 1 percent of the ADP-ribosyltransferase activity of the native toxin was constructed and was found to be deficient in pathogenic activities associated with B. pertussis including induction of leukocytosis, potentiation of anaphylaxis, and stimulation of histamine sensitivity. Moreover, this mutant strain failed to function as an adjuvant and was less effective in protecting mice from intracerebral challenge infection. These data suggest that the ADP-ribosyltransferase activity is necessary for both pathogenicity and optimum immunoprotection. These findings bear directly on the design of a nontoxic pertussis vaccine.

Topics: Adjuvants, Immunologic; ADP Ribose Transferases; Anaphylaxis; Animals; Antigens; Bordetella pertussis; Codon; Drug Tolerance; Histamine; Immunization; Leukocytosis; Macromolecular Substances; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mutation; Ovalbumin; Pentosyltransferases; Pertussis Toxin; Virulence Factors, Bordetella

Topics: Academic Dissertations as Topic; Acetylcholine; Acetylcholinesterase; Adenine Nucleotides; Adenosine Triphosphatases; Adrenal Medulla; Anaphylaxis; Animals; Calcium; Cytoplasm; Epinephrine; Exocytosis; Female; Guinea Pigs; Histamine; Histamine N-Methyltransferase; L-Lactate Dehydrogenase; Male; Microscopy, Electron; Monoamine Oxidase; Ovalbumin; Oxidoreductases Acting on CH-NH Group Donors

Carboplatin and carboplatin-ovalbumin mixture were examined for their antigenicity in Hartley guinea pigs as well as BALB/c and C3H/He mice in comparison with ovalbumin (OVA) and 2,4-dinitrochlorobenzene (DNCB)-OVA conjugate. The results obtained were as follows: 1. When guinea pigs were sensitized with carboplatin or carboplatin-OVA emulsified with Freund's complete adjuvant (FCA), these animals showed negative reactions in active systemic anaphylaxis (ASA), active cutaneous anaphylaxis (ACA), passive cutaneous anaphylaxis (PCA), passive hemagglutination (PHA) and Schultz-Dale test. 2. When mice were sensitized with carboplatin or carboplatin-OVA adsorbed to alum, these animals revealed a negative reaction in PCA using rats. 3. As positive controls, guinea pigs were sensitized with OVA or DNCB-OVA emulsified with FCA, and mice with OVA or DNCB-OVA adsorbed to alum. As a result, these animals disclosed positive reactions in ASA, ACA, PCA, PHA and Schultz-Dale test. As shown above, carboplatin was considered to possess neither antigenic nor haptenic properties. In addition, the dose levels of carboplatin employed in the present experiment were confirmed not to suppress immune reactions.

Topics: Anaphylaxis; Animals; Antigens; Carboplatin; Dinitrochlorobenzene; Guinea Pigs; Hemagglutination Tests; Immune Tolerance; Immunization; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Organoplatinum Compounds; Ovalbumin; Passive Cutaneous Anaphylaxis; Rats; Rats, Inbred Strains

The effects of muscarinic receptor stimulation by infusions of methacholine (6.25 x 10(-8) mol/min or 1.9 x 10(-7) mol/min) into isolated perfused, spontaneously beating sensitized guinea-pig hearts on the anaphylactic release of cysteinyl-leukotrienes (LT) and thromboxane (TX) B2 were investigated. Methacholine increased coronary flow and decreased heart rate under basal conditions. Furthermore, infusions of methacholine (1.9 x 10(-7) mol/min) significantly increased the anaphylactic release of TXB2 as well as of immunoreactive cysteinyl-LT, which were demonstrated by reversed phase high pressure liquid chromatography to consist of a mixture of LTC4, LTD4 and LTE4. Infusions of atropine (1.3 x 10(-7) mol/min) alone did not significantly affect coronary flow and heart rate prior to ovalbumin injection nor anaphylactic release of cysteinyl-LT. The anaphylactic release of TXB2 was, however, significantly decreased in the presence of atropine. Atropine (1.3 x 10(-7) mol/min) infused in addition to methacholine (1.9 x 10(-7) mol/min) abolished the effects of the muscarinic receptor agonist on spontaneous heart rate and significantly antagonized the increase in coronary flow prior to ovalbumin injection. Similarly, the simultaneous infusion of atropine abolished the effects of methacholine on the anaphylactic release of TXB2 and cysteinyl-LT. After antigen challenge hearts infused with methacholine, atropine or the combination of both drugs did not exhibit any differences with respect to anaphylactic changes of heart rate or the time course of anaphylactic coronary flow reduction. Thus, in the isolated perfused anaphylactic guinea-pig heart, muscarinic receptor stimulation significantly enhanced the release of the arachidonic acid-derived mediators TXB2 and cysteinyl-LT.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Anaphylaxis; Animals; Atropine; Guinea Pigs; Heart; Hemodynamics; Male; Methacholine Chloride; Methacholine Compounds; Myocardium; Ovalbumin; Receptors, Muscarinic; SRS-A; Thromboxane B2

In these studies we compared jejunal permeability to two probes--chromium 51-labeled ethylenediaminetetraacetic acid (51Cr-EDTA) (mol wt, 360) and ovalbumin (mol wt, 45,000)--under control conditions, during acute intestinal inflammation, and in response to systemic anaphylaxis. Acute inflammation was produced after infection with Nippostrongylus brasiliensis and rats were studied at day 0 (control), day 4 (early), day 10 (acute), and day 35 (postinfection). At the latter stage, immune rats were also studied during anaphylaxis induced by i.v. N. brasiliensis antigen. In each study, blood and urine were sampled over 5 h after the probes were simultaneously injected into ligated loops in anesthetized rats. In controls, small quantities (less than 0.04% and 0.002% of the administered dose for 51Cr-EDTA and ovalbumin, respectively) appeared in the circulation and plateaued at 1 h. During acute inflammation, the appearance of both probes continued to increase with time. Compared with controls, 5-h values for 51Cr-EDTA and ovalbumin were (a) significantly elevated at day 4 (p less than 0.005), (b) increased approximately 20-fold at day 10 (p less than 0.005 and less than 0.01, respectively), and (c) normal at day 35. Urinary recovery of 51Cr-EDTA followed the same pattern. During anaphylaxis, appearance of the probes in the circulation increased at 1 h to values approximately 10-fold those in controls (p less than 0.001 and less than 0.01, for 51Cr-EDTA and ovalbumin, respectively), and then declined. Urinary recovery of 51Cr-EDTA over 5 h was also significantly increased. We conclude that epithelial barrier function becomes impaired during both acute inflammation and anaphylaxis. In this rat model, gut permeability changes to 51Cr-EDTA reflect gut permeability changes to macromolecular antigens. If similar conditions exist in humans, urinary recovery of 51Cr-EDTA may be useful in monitoring intestinal abnormalities associated with inflammation.

Topics: Acute Disease; Anaphylaxis; Animals; Antigens, Helminth; Chromium Radioisotopes; Edetic Acid; Intestinal Diseases, Parasitic; Jejunal Diseases; Jejunum; Male; Nematode Infections; Nippostrongylus; Ovalbumin; Permeability; Rats; Rats, Inbred Strains

Three fractions (n-butanol, F2, and L5), isolated from an aqueous extract of Desmodium adscendens, a plant used in Ghana for the management of asthma, were evaluated for their pharmacological activity using ovalbumin and arachidonic acid-induced contractions of guinea pig airways. All three fractions inhibited the ovalbumin-induced contractions of indomethacin-pretreated tracheal spirals from sensitized animals dose dependently, but only L5 and n-butanol inhibited such contractions in the absence of indomethacin. The concentrations required to inhibit ovalbumin-induced contractions of lung parenchymal strips were threefold higher than with trachea. The contractile response over a 60-min period was divided into three phases. F2 and n-butanol inhibited all phases, whereas L5 inhibited only the late phase. n-Butanol and L5 inhibited arachidonic acid-induced contractions on indomethacin-pretreated tracheal spirals, a leukotriene-dependent reaction. There was no inhibition of arachidonic acid-induced contractions of lung parenchymal strips, which is largely a thromboxane-dependent reaction. The results suggest that D. adscendens contains several pharmacologically active substances that can inhibit allergic airway smooth muscle contraction at multiple sites, including the synthesis and (or) activity of the bronchoconstrictor leukotrienes.

Topics: 1-Butanol; Anaphylaxis; Animals; Arachidonic Acid; Arachidonic Acids; Butanols; Chemical Fractionation; Guinea Pigs; In Vitro Techniques; Indomethacin; Lung; Muscle Contraction; Ovalbumin; Plant Extracts; Plants, Medicinal; Trachea

The effect of antigen (ovalbumin) challenge on pulmonary hemodynamics, bronchoconstriction, and fluid filtration was investigated in Ringer's-perfused (non-recirculating) lungs that had been passively sensitized in vitro. Bolus ovalbumin injection (30 micrograms) produced immediate increases in pulmonary arterial pressure, peak intratracheal pressure, and lung weight within 1 min and secondary marked increases in intratracheal pressure and lung weight from 120 to 200 min. Electron microscopy of antigen-challenged isolated lungs showed evidence of both septal and intraalveolar edema. Ionophore A23187 (100 micrograms) challenge of nonsensitized lungs produced immediate pulmonary responses similar to antigen, whereas secondary increases in lung weight were smaller. Arachidonic acid pretreatment (1 microM) potentiated immediate antigen-induced increases in intratracheal pressure but did not affect pulmonary responses to ionophore challenge. Putative mediators of anaphylaxis including histamine, leukotrienes B4, C4, D4, and E4, platelet-activating factor, and substance P produced immediate changes in pulmonary arterial and/or intratracheal pressure similar to antigen challenge. Only platelet-activating factor and substance P partially mimicked the secondary edema formation noted following antigen challenge. Thus, antigen challenge in in vitro sensitized guinea pig lungs produced both immediate and secondary responses characterized by increases in vascular pressure, airway pressure, and edema formation. This occurred in the absence of circulating blood-formed elements and without a massive influx of cells. Synergism between mediators such as histamine, the leukotrienes, platelet-activating factor, and substance P released following antigen challenge may be necessary to produce the complete pathophysiological sequelae associated with antigen challenge in the perfused guinea pig lung.

Topics: Anaphylaxis; Animals; Antigens; Bronchi; Calcimycin; Constriction, Pathologic; Guinea Pigs; Hemodynamics; Immunization; In Vitro Techniques; Lung; Microscopy, Electron; Ovalbumin; Pulmonary Artery; Pulmonary Edema; Spasm

1. Ovalbumen (100 micrograms)-induced coronary vasoconstriction and decrease in cardiac developed tension were studied in isolated perfused hearts from sensitized guinea-pigs. Leukotriene-like material released in the cardiac effluent was assayed against synthetic leukotriene C4 (LTC4). 2. LTC4 was released in a time-dependent fashion, and release was enhanced when hearts were challenged in the presence of indomethacin (2.8 microM). The release was maximal at 2-3 min and detectable for as long as 10 min following ovalbumen challenge. Immunoreactive (ir) thromboxane-B2 (TxB2) was also detected in cardiac effluent which had been partially purified using C18 Sep-Paks. 3. CGS 8515 (0.03-1.0 microM), an inhibitor of 5-lipoxygenase, dose-dependently inhibited ovalbumen-induced coronary vasoconstriction and leukotriene-C4 release. CGS 8515 inhibited ovalbumen-induced decreases in cardiac developed tension at 0.3 and 1.0 microM, but did not antagonize coronary vasoconstriction induced by synthetic LTC4. 4. The release of cyclo-oxygenase products following ovalbumen challenge was not inhibited by CGS 8515, but was markedly inhibited by indomethacin (2.8 microM) pretreatment. 5. We conclude that leukotrienes have a major role in guinea-pig cardiac anaphylaxis, and that CGS 8515 has a cardio-protective action. The results obtained in these experiments in vitro show that CGS 8515 is a potent and selective 5-lipoxygenase inhibitor.

Topics: 4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; Anaphylaxis; Animals; Guinea Pigs; Heart; In Vitro Techniques; Lipoxygenase Inhibitors; Male; Naphthoquinones; ortho-Aminobenzoates; Ovalbumin; Perfusion; Prostaglandin-Endoperoxide Synthases; Pyrazoles; SRS-A

Intestinal motility was examined in an animal model of intestinal anaphylaxis. Hooded-Lister rats were sensitized (S) by intraperitoneal injection of 10 micrograms egg albumin (Ag) and compared with sham-sensitized controls (C). Seven days later three bipolar jejunal electrodes and a jejunostomy tube for motility recording and Ag administration were implanted. On day 14 intestinal myoelectric and motor activity were measured in fasted animals before and after intraluminal administration of either 10 mg egg albumin in 0.5 ml saline, 10 mg bovine serum albumin (BSA) in 0.5 ml saline, or placebo (P) challenge with 0.5 ml saline. Specific immunoglobulin E serum titers were greater than or equal to 1:64 in S animals, whereas C animals showed no response. None of the C animals challenged with P or Ag and none of the S animals challenged with P or BSA defecated after challenge, but all the S animals challenged with Ag developed diarrhea (P less than 0.001). In S animals challenged with Ag, the fasting motility pattern was disrupted, the migrating motor complex was abolished (P = 0.002), and the frequency of aborally propagating clustered contractions was increased (P less than 0.01). In this animal model an immune-mediated reaction to food protein was associated with diarrhea and altered intestinal myoelectric and motor activity.

Topics: Anaphylaxis; Animals; Chickens; Disease Models, Animal; Fasting; Food Hypersensitivity; Gastrointestinal Motility; Jejunum; Muscle, Smooth; Ovalbumin; Rats; Rats, Inbred Strains; Reference Values

Previous studies (V. J. Djurić, B. M. Marković, M. Lazarević, & B. D. Janković, 1987, in B. D. Janković, B. M. Marković, & N. H. Spector (Eds.), Neuroimmune interactions, pp. 561-568, New York: New York Acad. Sci.; B. M. Marković, V. J. Djurić, M. Lazarević, & B. D. Janković, 1988, Brain Behav. Immun. 2, 11-23) have shown that rats learn to associate the taste of saccharin with the induction of anaphylactic shock, thus exhibiting conditioned taste aversion (CTA) toward an otherwise preferred saccharin solution. The present experiment investigates the effect of unconditioned stimulus intensity (the amount of antigen used for the induction of shock) on CTA. Rats were sensitized to ovalbumin and subjected to a conditioning trial in which the conditioned stimulus (CS; saccharin solution given orally) signaled the presentation of the unconditioned stimulus (US; shocking doses of ovalbumin ranging from 0.5 to 3 mg given intraperitoneally). Behavioral signs, hematocrit, and rectal temperature were used for evaluation of anaphylactic shock. Twenty-four hours after the conditioning trial, rats were subjected to a two-bottle preference test between saccharin solution and water. Multiple regression statistical analysis revealed significant correlations among saccharin preference ratio, dose of antigen used for the induction of shock, behavioral signs of shock, rise in hematocrit, and fall in rectal temperature. A dose-dependent relation among saccharin preference ratio and physiological indicators of shock suggests that conditioned anaphylactic shock-induced avoidance behavior is functionally related to homeostatic factors involved in immune reactivity.

Topics: Anaphylaxis; Animals; Avoidance Learning; Conditioning, Classical; Dose-Response Relationship, Drug; Female; Male; Ovalbumin; Rats; Rats, Inbred Strains; Saccharin; Taste

1. The possible acute occurrence of airway hyperreactivity after immediate-type bronchial anaphylaxis has been investigated in anaesthetized guinea-pigs actively sensitized to ovalbumin (OA). 2. Aerosol challenge (OA 10 mg ml-1, 5 s) provoked immediate bronchoconstriction which was substantially, although incompletely, reversed by isoprenaline (Iso) infusion (1 microgram kg-1 min-1) for 10 min). 3. Bronchoconstrictor responses to 5-hydroxytryptamine (5-HT) were enhanced in challenged animals when compared to those in non-challenged animals that had also received Iso. This was seen as a leftward shift in the location of the dose-response curve for the bronchoconstrictor effect of 5-HT (dose-ratio 2.45, 95% confidence limits 1.77-3.38; P less than 0.01). This phenomenon was associated with pulmonary infiltration of polymorphonuclear leukocytes, which was not modified by Iso treatment. 4. Iso infusion alone caused a slight enhancement of airway reactivity seen as a small leftward shift of the dose-response curve for the bronchoconstrictor effect of 5-HT (dose-ratio 1.51, 95% confidence limits 1.07-2.13; P less than 0.05). 5. These results support a causal relationship between acute pulmonary inflammation and airway hyperreactivity in an animal model of human allergic asthma.

Topics: Airway Resistance; Anaphylaxis; Animals; Bronchi; Guinea Pigs; Isoproterenol; Lung; Male; Neutrophils; Ovalbumin; Respiratory Hypersensitivity; Serotonin

Topics: Anaphylaxis; Animals; Cardiac Output; Coronary Circulation; Female; Guinea Pigs; Heart; Histamine; Male; Ovalbumin

Topics: Anaphylaxis; Animals; Antibody Formation; Enkephalin, Leucine; Enkephalin, Methionine; Ovalbumin; Passive Cutaneous Anaphylaxis; Rats

Bronchoconstriction following the aerosolization of PAF-acether or antigen to guinea pigs induces autodesensitization, but the responses to direct spasmogenic substances are not modified. Bronchoconstriction by PAF-acether is not reduced when it is aerosolized to passively sensitized animals previously desensitized by repeated inhalations of the allergen (ovalbumin). In contrast, when passively sensitized animals are initially desensitized to PAF-acether by repeated inhalations of this agonist, ovalbumin aerosolization induces a bronchoconstriction which is significantly reduced when compared with the response obtained in nondesensitized animals though, in this case, the response to aerosolized histamine is not modified. Thus, PAF-acether is released during intrapulmonary anaphylactic shock induced by aerosolized ovalbumin and can be a prime candidate for its development.

Topics: Aerosols; Anaphylaxis; Animals; Antigens; Bronchial Spasm; Chromones; Desensitization, Immunologic; Female; Guinea Pigs; Histamine; Male; Ovalbumin; Platelet Activating Factor; Pyrilamine; Time Factors

Characteristics of the antigen-induced contraction of the isolated esophageal muscularis mucosae of actively sensitized guinea-pigs to ovalbumin (OA) were examined in vitro, and they were compared with those of compound 48/80- or polymyxin B-induced contraction. OA, above 0.01 microgram/ml, produced a sustained contraction of the sensitized esophageal muscularis mucosae, the amplitude of which was about 80-100% of the maximum contraction induced by carbachol (10 microM), while compound 48/80 and polymyxin B (10-300 micrograms/ml) produced less potent contractions of the non-sensitized esophageal muscularis mucosae. Contractions to OA or compound 48/80, but not to polymyxin B, were diminished by their repetitive applications. The contractile responses to OA, compound 48/80 and polymyxin B depended on the external calcium concentrations, and were abolished in the calcium-free medium. Pretreatment with tetrodotoxin (0.3 microM), atropine (0.3 microM), diphenhydramine (30 microM) or DSCG (300 microM) did not modify any of these contractions, whereas BW755C (100 microM) and quercetin (10 microM) significantly inhibited them. Indomethacin (10 microM) largely prevented only the polymyxin B-induced contraction, while FPL55712 (10 microM) inhibited both contractions to OA and compound 48/80. These findings indicate that the OA-induced anaphylactic contraction of the esophageal muscularis mucosae taken from the OA-sensitized guinea-pig may be an indirect action via the stimulation of releases of some mast cell-derived spasmogens. The spasmogens may involve the lipoxygenase products of arachidonic acid in part, but not histamine, acetylcholine or the cyclooxygenase products.

Topics: Anaphylaxis; Animals; Calcium; Carbachol; Esophagus; Female; Guinea Pigs; In Vitro Techniques; Mucous Membrane; Muscle Contraction; Muscle, Smooth; Ovalbumin; p-Methoxy-N-methylphenethylamine; Polymyxin B; Verapamil

Inhaled ozone was found to exert an enhancing effect for allergic lung sensitization when mice contracted an aerosolized allergen. The animals were exposed to ozone concentrations of 0.24, 0.16, 0.13, and 0.10 ppm. After 4 days of continuous ozone exposure, the mice had allergen contact from an aerosolized solution of ovalbumin. The animals were then maintained in ambient air for several days before the cycle of ozone and aerosolized allergen was repeated over four allergen contact cycles. Mice were rested in ambient air for a week after the last allergen contact, and they were then tested for allergic sensitization by the intravenous injection of 2 mg of ovalbumin to induce anaphylactic shock in allergic individuals. The control groups of mice were maintained in ambient air throughout the experiment, but they experienced identical allergen contact with the ozone-exposed mice. The phenomenon of allergic enhancement from ozone inhalation was detected at 0.24, 0.16, and 0.13 ppm of ozone. The enhancing effect disappeared at 0.10 ppm of ozone. The study indicated a potential for increasing the number of allergically sensitized individuals when various allergens are inhaled during periods of high ozone exposure with the consequent adverse changes on respiratory membranes. The significance to human health of the allergic enhancement phenomenon by ozone needs investigation.

Topics: Aerosols; Allergens; Anaphylaxis; Animals; Antigens; Female; Hypersensitivity; Lung Diseases; Ovalbumin; Ozone; Rats

The response of the rat proximal colon to an immunoglobulin E (IgE)-mediated hypersensitivity reaction was examined. Rats were sensitized to egg albumin (EA) by intraperitoneal injection, and serum titers of specific anti-EA IgE were measured at 14 days. Sensitized animals had titers of greater than or equal to 1:64, whereas no anti-EA IgE antibodies were detected in controls. Water and electrolyte absorption in the proximal colon, before and during antigen challenge, was measured by in vivo marker perfusion. Antigen challenge resulted in significant inhibition of water, Na+, Cl-, and K+ absorption in vivo. Proximal colonic tissue from sensitized and control animals was studied in Ussing chambers under short-circuited conditions. Antigen challenge of sensitized tissue resulted in significant increases in short-circuit current due to the induction of active Cl- secretion. No such changes were seen in control tissue. The abnormalities induced by antigen challenge in tissue from sensitized animals was blocked by doxantrazole (10(-3) M), a mast cell stabilizer. The findings indicate that IgE-mediated reactions in rat proximal colon to a food protein cause pertubations in water and electrolyte transport secondary to active Cl- secretion and these abnormalities appear to be due to mast cell degranulation.

Topics: Anaphylaxis; Animals; Antibody Formation; Colon; Epithelium; Female; Immunoglobulin E; In Vitro Techniques; Membrane Potentials; Ovalbumin; Rats; Rats, Inbred Strains; Reference Values

Intestinal anaphylaxis is associated with disturbances in gut function that are antigen-specific and dependent on mast cell degranulation. Using an animal model of intestinal anaphylaxis, we have correlated alterations in water and electrolyte transport, associated with intraluminal challenge, with specific intestinal mucosal mast cell degranulation by following systemic as well as local release of rat mast cell protease II. This protease is specific for intestinal mucosal mast cells and is known to selectively attack type IV collagen, which is found in basement membranes. Intraluminal antigen challenge in sensitized animals dramatically increased serum and intraluminal levels of rat mast cell protease II. Serum levels continued to rise throughout the duration of antigen challenge. Although light microscopy of challenged intestine demonstrated little distortion of mucosal architecture, ultrastructural examination revealed significant disruption to the basement membrane and underlying collagenous matrix of the intestinal mucosa. Our findings indicate that during mucosal immunoglobulin E-mediated reactions, rat mast cell protease II is released and is associated with ultrastructural changes in the intestinal mucosa. The systemic appearance of this specific protease provides a serum marker of intestinal anaphylaxis.

Topics: Anaphylaxis; Animals; Chymases; Female; Food Hypersensitivity; Immunoglobulin E; Intestinal Absorption; Intestinal Mucosa; Mast Cells; Microscopy, Electron; Ovalbumin; Rats; Serine Endopeptidases; Water-Electrolyte Balance

The release of prostaglandin D2 (PGD2), prostaglandin E2 (PGE2), and histamine induced by antigen and compound 48/80 was studied using an in vitro model of anaphylaxis in guinea pig skin. Abdominal skin from ovalbumin-sensitized guinea pigs was cut into 0.5-1.0 mm-thick slices which were incubated in Tyrode solution at 37 degrees C with or without either ovalbumin or 48/80. Released PGD2 and PGE2 were measured by radioimmunoassay and gas chromatography-mass spectrometry, respectively. Release of PGD2 was detectable at 2 min after challenge (50 micrograms/ml ovalbumin), reaching a maximum at about 15 min. Histamine release was more rapid, achieving 50% of maximum at about 4 min compared to about 7 min for PGD2. In 11 experiments incubation with ovalbumin (50 micrograms/ml for 10 min) induced a significant 6-fold increase in PGD2 compared to unchallenged controls (399 +/- 53 and 67 +/- 19 ng/g dry weight skin, respectively; mean +/- SEM) and a net 47.2% histamine release. In contrast, a smaller (27%) rise in PGE2 was found. Indomethacin (14 microns) completely suppressed evoked PGD2 and PGE2 synthesis without evident effect on histamine release, suggesting that the release of histamine in this model is not dependent on prostaglandin production. The mast cell degranulating agent compound 48/80 (50 micrograms/ml) released significant amounts of PGD2 (340 +/- 86 ng/g skin compared to 89 +/- 30 ng/g for control skin, n = 5) but had no appreciable effect on PGE2. These results show that guinea pig skin can synthesize significant quantities of PGD2 in anaphylactic reactions. Prostaglandin D2 produced in acute allergic reactions in skin in vivo may contribute to the inflammatory reaction, either directly or in synergism with other mediators.

Topics: Anaphylaxis; Animals; Antigens; Dinoprostone; Guinea Pigs; Histamine Release; Indomethacin; Mast Cells; Ovalbumin; p-Methoxy-N-methylphenethylamine; Prostaglandin D2; Prostaglandins D; Prostaglandins E; Skin

PAF-acether may be involved in anaphylaxis and asthma. We tested the new PAF-acether antagonist BN 52021 against the effects of antigen in passively sensitized guinea-pigs. Bronchoconstriction by ovalbumin administered i.v. (1 mg/kg) or by aerosol (1 or 10 mg/ml for a period of 1 min) was significantly reduced by BN 52021 (1-10 mg/kg), which did not inhibit drop of leukocyte counts after the i.v. challenge. In both cases, when the guinea-pigs were pretreated by propranolol, high amounts of BN 52021 became ineffective against shock. The reduction of the anaphylactic bronchoconstriction, induced by the combination of mepyramine, aspirin and FPL 55712 was not improved by BN 52021. Tested on isolated lung strips from passively sensitized guinea-pig, BN 52021, at a concentration which inhibits PAF-induced contraction (0.1 mM), did not inhibit the anaphylactic contraction triggered by the administration of ovalbumin (10 micrograms/ml) nor the accompanying release of histamine and thromboxane. In contrast, BN 52021 (30 microM) significantly reduced the anaphylactic release of histamine and of thromboxane from perfused lungs of passively sensitized guinea-pigs. The results with the isolated lung strips and the propranolol-treated guinea-pigs in vivo suggest a dissociation between the anti-anaphylactic and the anti-PAF-acether properties of BN 52021.

Topics: Airway Resistance; Anaphylaxis; Animals; Diterpenes; Female; Ginkgolides; Guinea Pigs; Histamine Release; In Vitro Techniques; Lactones; Lung; Male; Ovalbumin; Plant Extracts; Platelet Activating Factor; Thromboxane B2

Topics: Anaphylaxis; Animals; Bronchial Spasm; Capsaicin; Desensitization, Immunologic; Guinea Pigs; Male; Ovalbumin; Respiration; Substance P; Trachea

Topics: Anaphylaxis; Animals; Guinea Pigs; Histamine Release; In Vitro Techniques; Lung; Ovalbumin; Platelet Activating Factor

1. The combination of two methylation inhibitors 3-deazaadenosine (10(-4) or 4 x 10(-4) M) plus L-homocysteine (2 x 10(-4) M) caused a time-dependent inhibition of antigen-induced contraction, formation of thromboxane B2 (TxB2) and release of histamine from lung parenchyma strips taken from guinea-pigs actively sensitized with ovalbumin (OA). 2. The methylation inhibitors also prevented the lung strip contractions induced by the mediators platelet-activating factor (Paf-acether, 10(-6) M), leukotriene D4 (LTD4, 10(-8) and 3 x 10(-8) M), and in part to arachidonic acid (10(-6) and 10(-5) M), under conditions where the contractions to histamine (10(-6)-10(-4) M) were virtually unaffected. 3. TxB2 formation induced by these mediators or by OA was more affected by the methylation inhibitors than the lung strip contractions, indicating that prostaglandin formation is more sensitive to these inhibitors than the myotropic activity. In contrast, the suppressive effect of the methylation inhibitors on histamine secretion by parenchyma lung strips induced by OA followed the inhibition of the contraction. 4. These results show that inhibitors of methyltransferases interfere with the myotropic responses and with the release of mediators by actively sensitized guinea-pig lung strips stimulated with antigen, and suggest a major role for a methylation process in mediating the contraction of and mediator release by the lung parenchyma.

Topics: Adenosine; Airway Resistance; Anaphylaxis; Animals; Female; Guinea Pigs; Histamine Release; Homocysteine; In Vitro Techniques; Lung; Male; Methylation; Ovalbumin; Thromboxane B2; Tubercidin

Topics: Anaphylaxis; Animals; Fatty Acids, Unsaturated; Guinea Pigs; Leukotriene B4; Lung; Male; Ovalbumin; Platelet Activating Factor; SRS-A; Thromboxane B2

The effects of infusions of eicosapentaenoic acid (EPA) (6 X 10(-8) mol min-1 and 15 X 10(-8) mol min-1) on the coronary constriction and the release of immunoreactive sulphidopeptide-leukotrienes (SP-LT), thromboxane B2(TXB2) and 6-keto-prostaglandin F1 alpha (PGF1 alpha) from perfused anaphylactic guinea-pig hearts were investigated. EPA dose-dependently inhibited the profound early coronary flow reduction after antigen injection. The less pronounced late phase of anaphylactic coronary flow reduction was, however, not significantly affected. EPA (15 X 10(-8) mol min-1) significantly shortened the average duration of antigen-induced arrhythmias. EPA dose-dependently decreased release of immunoreactive TXB2 and 6-keto-PGF1 alpha from anaphylactic guinea-pig hearts. Release of immunoreactive SP-LT was dose-dependently increased after antigen challenge in the presence of EPA. Inhibiton of the release of SP-LT by the lipoxygenase inhibitor esculetin (1 X 10(-7) mol min-1) was accompanied by a significant attenuation of flow reduction during the late phase of anaphylactic vasoconstriction. Reversed phase h.p.l.c. of perfusates from anaphylactic guinea-pig hearts revealed immunoreactivity comigrating with authentic leukotriene C4 (LTC4), LTD4, and LTE4. In perfusates from hearts treated with EPA infusions, additional immunoreactivity was detected comigrating with LTC5, LTD5 and LTE5. In addition to immunoreactivity migrating with LTB4, as observed in control heart perfusates, in perfusates from EPA-treated hearts, a second peak was observed, which coincides with the retention time described for LTB5. Exogenous LTC5 (1 X 10(-12) mol min-1 and 20 X 10(-12) mol min-1) induced dose-dependent reductions of coronary flow and was found to be a slightly weaker constrictor than LTC4, but no significant differences were observed. Coronary vasoconstriction elicited by infusion of exogenous LTC4 (20 X 10(-12) mol min-1) was dose-dependently inhibited by infusions of EPA. However, the negative inotropic effect of LTC4 remained unaffected. Thus, in the isolated anaphylactic heart of the guinea-pig exogenous EPA was effectively metabolized via the 5-lipoxygenase pathway whereas the cyclo-oxygenase pathway of polyunsaturated fatty acid metabolism was found to be inhibited. The results are in agreement with the suggestion that cyclo-oxygenase products are mediators of the early phase of the anaphylactic coronary constriction, while vasoconstrictor SP-LT are involved in the lat

Topics: 6-Ketoprostaglandin F1 alpha; Anaphylaxis; Animals; Autacoids; Coronary Vessels; Eicosapentaenoic Acid; Guinea Pigs; Male; Myocardium; Ovalbumin; Radioimmunoassay; SRS-A; Thromboxane B2; Umbelliferones; Vasoconstriction

Antigenicity of terazosin was studied in the experimental animals and the following results were obtained. Terazosin was shown to be non-immunogenic in guinea-pigs and mice when immunized alone or with mixture of terazosin and protein as immunogen. Protein-conjugate of terazosin induced responses of hapten specific antibody when guinea pigs and mice were immunized. However, terazosin alone was shown to be not capable of eliciting any allergic responses. In conclusion, terazosin lacks immunogenicity and eliciting antigenicity in these experimental conditions and this suggests that drug allergic response would either not occur or be minimal, if any, when terazosin is administered clinically.

Topics: Adrenergic alpha-Antagonists; Anaphylaxis; Animals; Antigens; Drug Hypersensitivity; Female; Guinea Pigs; Immunoglobulin E; Male; Mice; Mice, Inbred Strains; Ovalbumin; Passive Cutaneous Anaphylaxis; Prazosin; Rats; Serum Albumin, Bovine; Species Specificity

In guinea pigs sensitized with 1 microgram ovalbumin together with 100 mg Al(OH)3, somatostatin levels were selectively increased up to two and 3 times in tissue extracts from trachea and bronchi, respectively, but not in lung as compared to controls. The increase of somatostatin levels observed in trachea and bronchi after sensitization was associated with a decrease in the binding capacity of both high- and low-affinity binding sites (without changes in the affinity values) in the corresponding cytosolic fractions. These results suggests that an increase in airways somatostatin content may be involved in the pathogenesis of anaphylactic bronchoconstriction.

Topics: Anaphylaxis; Animals; Bronchi; Constriction, Pathologic; Cytosol; Guinea Pigs; Immunization; Lung; Male; Ovalbumin; Receptors, Neurotransmitter; Receptors, Somatostatin; Somatostatin; Trachea

Topics: Aluminum Hydroxide; Anaphylaxis; Animals; Avoidance Learning; Conditioning, Psychological; Female; Ovalbumin; Rats; Rats, Inbred Strains; Taste

We describe in this paper a simple aerosol method of provoking bronchial anaphylaxis in both anesthetized guinea pigs and guinea pig isolated lungs. We also show the time course of bronchoconstriction induced by an aerosol of ovalbumin in previously sensitized guinea pigs in vivo and in vitro and the effect of the H1 antagonist mepyramine on this bronchoconstriction. We believe this method of inducing anaphylaxis is important, since the antigen is delivered via a more relevant route, i.e., the airways. Furthermore, the in vitro technique should greatly facilitate the analysis of the anaphylactic mediators released in guinea pig lung following inhalational challenge.

Topics: Aerosols; Anaphylaxis; Animals; Guinea Pigs; Hemodynamics; Male; Ovalbumin; Pyrilamine; Respiratory Function Tests

Newborn mongrel dogs were sensitized with conjugates of ovalbumin (OA) and 2,4-dinitrophenol (OA-DNP3) in the presence of Al(OH)3 to produce high levels of anti-OA and anti-DNP IgE antibody. At 4-6 months of age, when anti-DNP and anti-OA antibody levels reached titers of 64 by passive cutaneous anaphylaxis, the dogs underwent separate inhalation and intravenous challenges with conjugates of DNP and bovine gamma globulin (DNP15-BGG) and OA. Inhalation challenge with DNP15-BGG and OA resulted in 5- and 10-fold increases in airflow resistance, respectively. Intravenous challenge with either DNP15-BGG or OA produced profound anaphylaxis with 60-80% decreases in blood pressure, cardiac output and regional blood flows in the carotid, superior mesenteric and renal arteries, and the distal aorta. Treatment of sensitized dogs with 5 doses of 20 mg of conjugates of DNP and polyvinyl alcohol (DNP2-PVA) on alternate days resulted in suppression of anti-DNP IgE antibody production; abrogation of established airway and vascular anaphylactic sensitivities; no change in regional blood flows, and no effect on sensitivities to challenge with OA.

Topics: 2,4-Dinitrophenol; Anaphylaxis; Animals; Bronchial Provocation Tests; Bronchial Spasm; Dinitrophenols; Disease Models, Animal; Dogs; Haptens; Immunoglobulin E; Immunosuppression Therapy; Ovalbumin; Regional Blood Flow

The influence of aerosolized azelastine on acute lung anaphylaxis in actively sensitized guinea pigs (experimental asthma model) was studied. Azelastine administered as an aerosol produced significant inhibition of acute lung anaphylactic responses, ie, the reduction in dynamic lung compliance and an increase in pulmonary airway resistance. These data showed that regardless of the method of sensitization and time of administration (immediately or 15 minutes before antigen challenge), aerosolized azelastine affords significant protection against acute lung anaphylaxis. The inhibition of acute lung anaphylaxis by aerosolized azelastine in the guinea pig asthma model may be due to (1) inhibition of the synthesis/release of chemical mediators, eg, histamine and leukotrienes, etc and/or (2) antagonism of the pharmacologic mediators at the receptor site in respiratory smooth muscles.

Topics: Aerosols; Anaphylaxis; Animals; Antigens; Asthma; Disease Models, Animal; Guinea Pigs; Injections, Intraperitoneal; Injections, Intravenous; Lung; Male; Ovalbumin; Phthalazines; Pyridazines

WEB 2086, a novel specific platelet activating factor (PAF) antagonist derived from triazolodiazepines, inhibited in a dose-related manner the PAF-dependent component of anaphylaxis as well as PAF-induced effects in mice and guinea pigs. In mice a lethal anaphylactic shock and a PAF-induced (100 micrograms/kg i.v.) death was inhibited by i.v. WEB 2086. The ED50 values were 13.6 and 0.37 mg/kg i.v., respectively. In actively sensitized guinea pigs, the anaphylactic lung reaction (bronchoconstriction), but not the corresponding hypotension, was prevented by oral (0.05-0.5 mg/kg) doses of WEB 2086. In contrast, in passively sensitized animals a dose-dependent inhibition of the pulmonary (bronchoconstriction) and blood pressure (hypotension) reaction due to anaphylaxis was achieved by i.v. WEB 2086. Similarly, oral (0.05-0.5 mg/kg) and i.v. (0.005-0.05 mg/kg) WEB 2086 inhibited PAF-induced reduction in respiratory flow (bronchoconstriction) and hypotension in guinea pigs. The ED50 values were 0.070 and 0.066 mg/kg p.o., and 0.017 and 0.015 mg/kg i.v., respectively. In conclusion, PAF seems to play a more major role in passive than in active anaphylaxis in guinea pigs. These results provide further evidence for an important role of PAF in anaphylaxis and support the hypothesis that PAF is involved in asthma and other allergic diseases.

Topics: Administration, Oral; Anaphylaxis; Animals; Azepines; Blood Pressure; Guinea Pigs; Immunization; Immunization, Passive; Injections, Intravenous; Male; Mice; Ovalbumin; Platelet Activating Factor; Pyrilamine; Respiration; Triazines; Triazoles

Anaphylactic bronchoconstriction provoked by aerosol challenge, and its pharmacological modulation, has been investigated in anaesthetized pump-ventilated guinea-pigs actively sensitized to ovalbumin (OA). Aerosol challenge (OA 0.03-10 mg ml-1) provoked immediate bronchoconstriction, the degree of which, and its rate of development, was directly related to antigen concentration. Concomitant changes in heart rate and systemic arterial blood pressure following aerosol challenge were reduced compared with systemic (OA, 1 mg kg-1 i.v.) challenge. Unlike systemic challenge, aerosol challenge did not cause a concomitant fall in either circulating leukocyte or platelet count. When a submaximal (microshock) aerosol challenge stimulus (OA, 0.3 mg ml-1, 5 s) was employed, bronchoconstriction was markedly reduced by mepyramine (2 mg kg-1 i.v.). The residual component of bronchoconstriction was enhanced by indomethacin (10 mg kg-1 i.v.), an effect which was reversed by either BW755C (30 mg kg-1 i.v.) or FPL55712 (10 mg kg-1 i.v.). When a supramaximal (macroshock) aerosol challenge stimulus (OA, 10 mg ml-1, 5 s) was employed, bronchoconstriction was also markedly reduced by mepyramine. Residual bronchoconstriction was not altered by indomethacin, slowed but not reduced by indomethacin plus BW755C, and substantially reduced by indomethacin plus FPL55712. The successive incremental antagonism of anaphylactic bronchoconstriction by mepyramine and mepyramine plus indomethacin and FPL55712 indicates that the predominant mediators involved are histamine and leukotrienes, respectively. The failure of indomethacin plus BW755C to inhibit the mepyramine-resistant bronchoconstriction provoked by OA macroshock may reflect the increased generation of leukotrienes via a 5-lipoxygenase isoenzyme resistant to inhibition by BW755C. 7. Aerosol challenge of actively sensitized anaesthetized guinea-pigs by this method may be a useful model of human allergic bronchoconstriction, particularly when the effects of a drug given itself as an aerosol are being evaluated.

Topics: Aerosols; Allergens; Anaphylaxis; Anesthesia; Animals; Bronchi; Guinea Pigs; Hemodynamics; Male; Ovalbumin; Respiratory Function Tests

Inbred guinea pigs selected for high (IMM/S) respectively low (IMM/R) responsiveness to ovalbumin (OA) as measured by induced respiratory anaphylaxis, were investigated for atopic immune responses of their conjunctival mucosa. IMM/S animals sensitized either by inhalation of OA, or by instillation of antigen into the conjunctival sac, developed regularly an acute ocular inflammatory response to topical (conjunctival) challenge with the allergen. A minimum of 1 microgram OA dropped repeatedly into the conjunctival sac was enough for both ocular and systemic sensitization of the animals, but the minimal dose of effective challenge was considerably higher. In IMM/R animals, ocular hypersensitivity was not achieved by inhalation of OA, but after topical administration of the antigen some of the IMM/R strains could be challenged to ocular anaphylactic responses of the same intensity as observed in IMM/S animals. The conjunctivae of both IMM/S and IMM/R animals could be sensitized passively by intraperitoneal injection of guinea pig sera containing homocytotropic antibodies to OA, but topical administration of such sera had no effect.

Topics: Administration, Inhalation; Administration, Topical; Anaphylaxis; Animals; Antibodies; Bronchi; Bronchial Provocation Tests; Conjunctiva; Conjunctivitis, Allergic; Dose-Response Relationship, Immunologic; Guinea Pigs; Immunization; Ovalbumin; Respiratory Hypersensitivity

Wistar rats were sensitized for anaphylactic shock with ovalbumin and treated intraperitoneally with 10 injections of methionine-enkephalin and leucine-enkephalin (4 mg/kg of body weight). Both pentapeptides suppressed the development of systemic anaphylaxis after intravenous injection of a shocking dose of ovalbumin. Methionine-enkephalin completely protected the animals from fatal shock. The level of circulating IgE and precipitating anti-ovalbumin antibodies decreased in rats given 10 injections of enkephalins. Mast cell degranulation was significantly inhibited in these animals as observed at autopsy. A single intraperitoneal injection of 4 mg/kg body weight of methionine-enkephalin given 30 min before the challenge with shock-inducing dose of antigen was also effective, although to a lesser extent, in protecting animals from anaphylactic shock. One injection of leucine-enkephalin did not exhibit significant antishock activity. The results suggest that enkephalins, and methionine-enkephalin in particular, are potent modulators of the complex biochemical processes underlying the anaphylactic shock in the rat.

Topics: Anaphylaxis; Animals; Enkephalin, Leucine; Enkephalin, Methionine; Enkephalins; Immunoglobulin E; Male; Mast Cells; Ovalbumin; Rats; Rats, Inbred Strains

Topics: Administration, Inhalation; Anaphylaxis; Animals; Bronchi; Eosinophils; Epithelium; Guinea Pigs; Immunization, Passive; Injections, Intravenous; Male; Models, Biological; Ovalbumin

The effects of mediator antagonists and synthesis inhibitors on anaphylactic responses of lung parenchymal strips from ovalbumin-sensitized guinea-pigs have been investigated. The dependence of the responses on the concentration of the antigen has been studied using a cumulative concentration-response technique. Anaphylactic contraction and histamine release were similar in response to cumulative and single additions of ovalbumin. Contractile responses to high doses of antigen (1 and 10 micrograms/ml) were slightly inhibited by mepyramine, whereas those to low doses (0.01 microgram/ml) were inhibited by leukotriene antagonist FPL 55712 and the lipoxygenase inhibitors nordihydroguaiaretic acid and BW 755C. Indomethacin potentiated both histamine release and contraction induced by ovalbumin. It is concluded that leukotrienes play a major role in anaphylactic responses to low antigen concentrations. Such responses may more closely resemble allergic bronchoconstriction in man. Histamine has a minor role in responses to higher antigen concentrations, where the major mediator of the responses may also be leukotrienes. This possibility cannot be proved with currently available leukotriene antagonists and synthesis inhibitors.

Topics: Anaphylaxis; Animals; Antigens; Chromones; Female; Guinea Pigs; Histamine Release; In Vitro Techniques; Lung; Ovalbumin; Pyrilamine

Indomethacin potentiates antigen-induced contraction and histamine release in lung parenchymal strips from ovalbumin-sensitized guinea-pigs. Mepyramine and the leukotriene antagonist FPL 55712 did not affect the potentiating effect of indomethacin on anaphylactic contraction, but two lipoxygenase inhibitors, BW 755C and nordihydroguaiaretic acid, abolished it. FPL 55712 inhibited contractile responses to leukotriene D4, but not those to leukotriene C4. The potentiation of histamine release by indomethacin was unaffected by the lipoxygenase inhibitors. It is concluded that a lipoxygenase product, possibly leukotriene C4, mediates the potentiation of contraction by indomethacin; the enhancement of histamine release, however, involves a different mechanism, possibly inhibition of the production of inhibitory prostaglandins.

Topics: 4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; Anaphylaxis; Animals; Chromones; Female; Guinea Pigs; Histamine Release; In Vitro Techniques; Indomethacin; Lung; Muscle Contraction; Muscle, Smooth; Ovalbumin; Pyrazoles; SRS-A

Rats were immunized intraperitoneally with ovalbumin and the disappearance of bromthymol blue (BTB) from the intestinal lumen, its accumulation in the tissue, and its net absorption were examined by means of an in-situ recirculation technique during local anaphylaxis. The disappearance of BTB from the intestinal lumen and its net absorption were significantly reduced, but there was no significant effect on its accumulation in the tissue. The pH value of the luminal solution and the perfusate volume were not influenced by intraluminal challenge with the antigen in ovalbumin-immunized rats. In addition, no significant effect was observed on intestinal permeability to BTB in the in-vitro everted sac technique. The intestinal blood flow, measured by a hydrogen clearance method, was not reduced significantly by the intraluminal exposure to antigen. There was enhanced Evans Blue leakage and mucus release in the perfusate after intraluminal challenge with ovalbumin in ovalbumin-immunized rats, but not in non-immunized rats. A significant increase of BTB binding with macromolecular substances in the perfusate was observed during the local anaphylaxis. These findings suggest that the decreased absorption of BTB is due to the interaction with the macromolecular substances in the perfusate during local anaphylaxis.

Topics: Anaphylaxis; Animals; Bromthymol Blue; Digestive System; Evans Blue; Hydrogen-Ion Concentration; Intestinal Absorption; Intestines; Male; Mucus; Ovalbumin; Pharmaceutical Preparations; Rats; Rats, Inbred Strains; Regional Blood Flow; Thymol

Ovalbumin was used to trigger passive systemic anaphylactic shock in guinea-pigs treated with serum provided by actively sensitized animals. Shock was characterized by bronchoconstriction and hypotension, accompanied by leukopenia and moderate thrombocytopenia. Neither aspirin, a cyclooxygenase inhibitor, FPL 55712, a peptido-leukotriene antagonist, nor their combination interfered with shock, under conditions where the selective histamine antagonist mepyramine, up to 20 micrograms/kg, suppressed bronchoconstriction. When the animals were treated with the beta-adrenergic antagonist propranolol, mepyramine lost its activity, even if combined with aspirin and FPL 55712. Lungs provided by the sensitized animals secreted histamine and formed thromboxane A2 when challenged with ovalbumin, but failed to do so when the lungs were collected after systemic shock; demonstrating that in vivo desensitization involves direct effects on the lungs. Parenchyma lung strips from the sensitized animals and lung strips and trachea from non-sensitized animals placed together in an organ bath contracted when exposed to the antigen in presence of mepyramine. The contraction of the sensitized strips was not affected by FPL 55712 nor by the lipoxygenase inhibitors nordihydroguarietic acid and BW755c, but the responses of the non-sensitized tissues were suppressed, demonstrating that, apart from peptido-leukotrienes, parenchyma lung strips from passively sensitized animals generate a leukotriene and histamine-independent contracting activity. Histamine and peptido-leukotrienes do not account for the totality of passive anaphylactic shock in the guinea-pig.

Topics: Anaphylaxis; Animals; Aspirin; Chromones; Female; Guinea Pigs; Histamine H1 Antagonists; In Vitro Techniques; Lung; Male; Muscle Contraction; Ovalbumin; Propranolol; Pyrilamine; SRS-A

The effects of clonidine on the bronchospastic responses induced by vagal stimulation or antigen challenge were studied in anaesthetized guinea-pigs. Electrical stimulation of the vagus nerves by 2-4 Hz induced a vigorous, mainly atropine-sensitive bronchoconstriction, which was strongly inhibited by clonidine (0.05 mg/kg i.v.). The inhibitory effect of clonidine was significantly reduced by the alpha 2-adrenoceptor antagonist yohimbine (1 mg/kg i.v.). Another series of experiments was done with ovalbumin-sensitized guinea-pigs. Respiratory anaphylaxis was induced by antigen inhalation resulting in an increase of pulmonary resistance from 100% (baseline) to about 190% in the control group. Animals pretreated with a clonidine aerosol (0.03%) showed a marked inhibition of the bronchospastic response. It is suggested that the inhibition of the bronchospastic responses induced by clonidine may be mediated by a stimulation of alpha 2-adrenoceptors, which exerts an inhibitory control of the excitatory vagal activity in the guinea-pig airways.

Topics: Anaphylaxis; Animals; Antigens; Bronchial Spasm; Clonidine; Electric Stimulation; Guinea Pigs; Immunization; Male; Ovalbumin; Receptors, Adrenergic, alpha; Vagus Nerve

The influence of an anaphylactic challenge on the relaxing effects of isoproterenol, prostaglandin E1 (PGE1), forskolin, and aminophylline was examined using an isolated tracheal muscle preparation from ovalbumin (OA)-sensitized guinea pigs. As compared with histamine (4 X 10(-5) M) challenge, an anaphylactic challenge with OA (5 micrograms/mL) caused a rightward shift of the concentration-response curves for isoproterenol, PGE1, and forskolin but not for aminophylline. Their 50% effective concentrations were increased by about 1.7- to 2.8-fold of the histamine challenged preparations. These results indicate that anaphylactic challenge of the sensitized guinea pig tracheal muscle diminishes relaxing effects of isoproterenol, PGE1, and forskolin but not aminophylline. Possible mechanisms of these subsensitivities may involve both impaired coupling mechanism between receptor and adenylate cyclase and decreased adenylate cyclase activity, rather than their receptor numbers or affinity.

Topics: Alprostadil; Aminophylline; Anaphylaxis; Animals; Colforsin; Guinea Pigs; In Vitro Techniques; Isoproterenol; Male; Muscle Relaxation; Muscle, Smooth; Ovalbumin; Receptors, Adrenergic, beta; Trachea

Bradykinin (BK) is widely believed to play a role in the pathogenesis of anaphylaxis. To help clarify any such roles, we examined for effects of inhibitors of kininase II (angiotensin converting enzyme, ACE) and "kininase I" (carboxypeptidase N, CPN), on the early course of egg albumin-induced aggregate anaphylaxis in anesthetized guinea pigs. In this model, pulmonary and systemic arterial blood pressure (BP) rise (unless pulmonary fibrillation occurs), lung wgt increases by approximately 60% and pulmonary microvessels are occluded by cell-rich thrombi, all within 5 min of i.v. antigen. The 30 min mortality rate is approximately 2%. ACE inhibitors (BPP9a, Captopril and MK 422; doses up to 140 mumol/kg) do not make anaphylaxis more nor less severe in terms discernible by changes in BP, lung wgt, EKG or intravascular coagulation. In marked contrast, an inhibitor of CPN (2-mercaptomethyl-3-guanidinoethylthiopropionic acid, 2-MGP; 8-16 mumol/kg) increases the 30 min mortality rate to 94% and lung wgt to 180% of control. The animals die in ventricular fibrillation. Given the enormous BK potentiating effects of BPP9a, Captopril and MK 422, it seems likely that little if any BK is formed in the early min of anaphylaxis. 2-MGP does not potentiate BP effects of BK but markedly potentiates effects of C3a anaphylatoxin. Thus, our data support the views that BK is neither a primary nor secondary mediator of aggregate anaphylaxis, and the adverse effects of 2-MGP are best explained in terms of preservation of anaphylatoxins and not in terms of preservation of kinins.

Topics: 3-Mercaptopropionic Acid; Anaphylaxis; Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Captopril; Carboxypeptidases; Enalapril; Enalaprilat; Guinea Pigs; Lung; Lysine Carboxypeptidase; Ovalbumin; Sulfhydryl Compounds

LTB4 is a potent chemotactic and chemokinetic eicosanoid released by leukocytes during inflammatory reaction; in addition to this it possesses a bronchopulmonary activity in different animal species. Since cysteinyl containing leukotrienes and other eicosanoids have been shown to induce hyperreactivity of pulmonary smooth muscles, we investigated the release of LTB4 from different anatomical structures of guinea-pig lung in vitro and the possible interaction with histamine in these tissues. In fact, hyperreactivity is evidentiated by a synergism between different mediators. The ovalbumin sensitized guinea-pig lung has been brushed in order to separate lung parenchyma from bronchi and vessels which were divided into large and small preparations. The antigen challenge resulted in a statistically significant increase in LTB4 production in large bronchi and vessels, whereas in the other preparations considered the basal levels of the eicosanoid were not modified during the anaphylactic reaction. In parallel with the differential site of LTB4 release, a positive interaction between LTB4 and histamine was only observed in the pulmonary artery. These data suggest that the possible role of LTB4 in different pulmonary diseases is not confined to the airway smooth muscle but it might be related to its capacity to induce vascular hyperreactivity.

Topics: Anaphylaxis; Animals; Guinea Pigs; Histamine; In Vitro Techniques; Leukotriene B4; Lung; Male; Muscle Contraction; Ovalbumin; Pulmonary Artery

The pathophysiology of anaphylaxis is very complex, and the sequelae of events are not fully explained in terms of the effects of histamine and peptide leukotrienes alone. Platelet-activating factor (1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine, PAF-acether) has been detected in animals undergoing anaphylaxis. Injection of synthetic PAF-acether induces similar effects, including bronchoconstriction, respiratory arrest, systemic hypotension, neutropenia, and thrombocytopenia. The results reported here demonstrate that the histamine- and leukotriene-independent component of guinea pig anaphylaxis in vivo and in isolated lung parenchymal strips in vitro is mediated by PAF-acether. However, PAF-acether is not responsible for the anaphylaxis-induced thrombocytopenia.

Topics: 4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; Alprazolam; Anaphylaxis; Animals; Anti-Inflammatory Agents; Benzodiazepines; Blood Pressure; Diphenhydramine; Guinea Pigs; In Vitro Techniques; Kinetics; Lung; Male; Ovalbumin; Platelet Activating Factor; Platelet Count; Pyrazoles

We examined the effects of glucocorticosteroids (GCS) on antigen-induced bronchial anaphylactic reactions (BAR) in SD rats immunized with ovalbumin (OA) and alum. The animals were treated with vehicle, budesonide (BUD), dexamethasone (DEX), or hydrocortisone (HC) at various times before intravenous (i.v.) antigen challenge. The drugs were administered either intraperitoneally (i.p.) or intratracheally (i.t.); the BAR was elicited by a low or by a high challenge dose of antigen. A BAR elicited by a low challenge dose of antigen was reduced in a dose-dependent way by all GCS after i.p. administration; at 1 mg/kg, BUD and DEX significantly reduced BAR and at 50 mg/kg all three of the examined compounds inhibited the BAR by 50% or more. For BUD, maximum effect was recorded when it was given 12 h before test. There was only a slight variation in the inhibitory effects of the GCS with immunization conditions of test animals. I.t. instillation of the drugs did not markedly increase their inhibitory capacity as compared to i.p. administration. BAR elicited by a high antigen dose was at best marginally affected by the GCS when given either i.p. or i.t. Thus, antigen-induced airway reactivity in rats can be reduced by GCS treatment provided that this is performed sufficiently long before the test and that the challenge dose of antigen is not too high.

Topics: Acetophenones; Administration, Topical; Alum Compounds; Aluminum; Anaphylaxis; Animals; Antigens; Bronchial Diseases; Budesonide; Cromolyn Sodium; Dexamethasone; Dose-Response Relationship, Drug; Drug Interactions; Glucocorticoids; Immunization; Injections, Intraperitoneal; Injections, Intravenous; Male; Ovalbumin; Pregnenediones; Quinacrine; Rats; Rats, Inbred Strains; Respiration; Sulfates; Time Factors

The effects of a new Platelet-Activating Factor (PAF-acether) antagonist (BN 52021) extracted from Ginkgo biloba leaves have been studied on the release of metabolites of arachidonic acid in IgG-dependent guinea pig pulmonary anaphylaxis in vitro. Prostaglandin E2 (PGE2) and thromboxane B2 (TxB2) were assayed using a novel ELISA technique. The release of PGE2 and TxB2 from anaphylactic lungs reached a maximum 4-5 min following the antigen challenge (about 3.2 and 31.0 ng/ml respectively) and decayed slowly during the following 25 min. BN 52021 (1, 3 and 30 micrograms/ml) produced dose-dependent decreases of the release of PGE2 and TxB2. These results suggest that there are some interactions between the release of icosanoids and PAF-acether in anaphylaxis.

Topics: Anaphylaxis; Animals; Arachidonic Acid; Arachidonic Acids; Dinoprostone; Diterpenes; Female; Ginkgolides; Guinea Pigs; In Vitro Techniques; Kinetics; Lactones; Lung; Male; Ovalbumin; Plant Extracts; Platelet Activating Factor; Prostaglandins; Prostaglandins E; Thromboxane B2; Thromboxanes

The ability of injected rat IgE myeloma protein IR162 to inhibit passive and active cutaneous anaphylaxis in Lewis rats was investigated. IgE injected i.p. 24 hr before the sensitization with IgE anti-ovalbumin (OVA) completely inhibited both IgE- and IgG2a-induced passive cutaneous anaphylactic (PCA) reactions at a dose (2.5 mg/100 g body weight) that resulted in peak serum concentrations of 150 micrograms IgE IR162/ml. Peak IgE IR162 serum concentrations of 20 to 60 micrograms/ml inhibited the PCA reaction in approximately 50% of the rats. Intracutaneous injection of a mixture of myeloma IgE and anti-OVA IgE in a ratio of 100:1 or more also inhibited the PCA reaction. In contrast, the PCA reaction was not inhibited by seven daily doses of IgE beginning 24 hr after passive sensitization. Likewise, the cutaneous anaphylactic reaction elicited in rats 14 days after immunization with OVA and Bordetella pertussis was not prevented by daily injections of myeloma IgE despite a 1000- to 3000-fold excess of the myeloma IgE to anti-OVA IgE serum concentration. The data demonstrate that parenteral administration of myeloma IgE inhibits the PCA reaction only when given before passive sensitization and does not prevent cutaneous anaphylaxis in actively immunized rats. Because myeloma IgE failed to inhibit anaphylactic reactions in actively immunized rats, it is questionable whether administering human IgE-derived synthetic peptides or recombinant DNA-produced IgE fragments will be able to prevent allergic diseases by blocking the IgE Fc receptors on mast cells.

Topics: Anaphylaxis; Animals; Immunity, Active; Immunization, Passive; Immunoglobulin E; Injections, Intraperitoneal; Myeloma Proteins; Ovalbumin; Passive Cutaneous Anaphylaxis; Rats; Rats, Inbred BN; Rats, Inbred Lew; Skin; Time Factors

The involvement of platelet activating factor (PAF) in anaphylaxis was examined by recording the pulmonary responses of anesthetized passively sensitized guinea-pigs to the aerosolization of ovalbumin. Animals were tested with and without BN 52021 (a ginkgolide B, PAF receptor antagonist) pretreatment. Aerosolization of ovalbumin produced a bronchoconstriction (BC) which could be made refractory to additional challenges with the antigen. In animals desensitized to ovalbumin, aerosolization of PAF produced an unattenuated BC. Guinea pigs desensitized by repeated aerosolizations of PAF subsequently showed reduced responses to aerosolized antigen suggesting that PAF may be involved in the BC. Animals pretreated with BN 52021, were protected against the effects of systemically administered PAF and also showed reduced responses to aerosolized antigen. Aerosolization of the leukotriene antagonist, FPL 55712, was ineffective against anaphylactic BC under conditions where catecholamine and histamine release were blocked.

Topics: Aerosols; Anaphylaxis; Animals; Blood Platelets; Diterpenes; Female; Ginkgolides; Guinea Pigs; Immunoglobulin E; Lactones; Male; Neutrophils; Ovalbumin; Plant Extracts; Platelet Activating Factor; Propranolol

We studied the effects of anti-asthmatic and anti-inflammatory drugs on antigen-induced bronchial anaphylactic reactions (BAR) in Sprague Dawley (SD) rats immunized with ovalbumin (OA) and alum. The animals were treated locally (intratracheal instillation (i.t.) or by aerosol) with terbutaline (TERB), disodium cromoglycate (DSCG), theophylline (THEO), the xanthine derivative 3,7-dihydro-1,8-dimethyl-3-phenyl-1H-purine-2,6-dione (D4026), budesonide (BUD) or dexamethasone (DEX) at various times before intravenous (i.v.) challenge with OA. The BAR was elicited by giving a low dose of OA. When the response to that challenge had levelled an additional high dose of antigen was given. Previous work had shown that TERB, DSCG, and D4026 given systemically (i.v.) at a suboptimal dose, had a better inhibitory efficacy when the animals were challenged with a low antigen dose late (6 weeks) than when challenged early (2-3 weeks) after immunization. We show here that such a difference in efficacy is not recorded after local treatment. Moreover, each of the drugs inhibited BAR to the same extent after i.t. as after i.v. treatment. Potent drugs like TERB and D4026 seemed to show similar efficacy when given either i.t. or by aerosol, whereas less potent drugs like DSCG and THEO were less effective when given by aerosol. In a previous study, we showed that the inhibitory capacity of glucocorticoids (GCS) on the BAR did not vary with sensitization conditions of the rats, BUD and DEX showed the same inhibitory capacity after intraperitoneal (i.p.) treatment as after i.t. treatment. In the present study, DEX showed increased whereas BUD showed decreased inhibitory capacity when given by aerosol 18-24 h before challenge. The duration of the anti-anaphylactic activity after inhalation was longer for DEX than for BUD.

Topics: Administration, Inhalation; Anaphylaxis; Animals; Antigens; Bronchi; Bronchodilator Agents; Glucocorticoids; Male; Ovalbumin; Rats; Trachea

Admixtures of free antigens have been shown to play the main role in the anaphylactogenic danger of vaccines. The immunogenic and anaphylactogenic action of such antigenic admixtures in corpuscular influenza vaccine can be observed after the immunization of animals in 2 or 3 injections. Host antigens incorporated into viral particles induce no anaphylactic reaction in guinea pigs after their immunization in 3 injections.

Topics: Anaphylaxis; Animals; Chick Embryo; Drug Contamination; Guinea Pigs; Influenza Vaccines; Ovalbumin; Rabbits; Vaccination

Topics: Anaphylaxis; Animals; Bronchi; Guinea Pigs; Histamine; Methylprednisolone; Ovalbumin; SRS-A

Topics: Anaphylaxis; Animals; Guinea Pigs; In Vitro Techniques; Lung; Muscle Contraction; Ovalbumin; SRS-A

The genetic and immunological basis of respiratory anaphylaxis was studied in two strains of guinea pigs selectively bred for either high or low respiratory anaphylactic response to inhalation of ovalbumin. Individuals of the parental strains, F1-hybrids and backcross offspring were examined for class II MHC type and asthmatic response to ovalbumin. Analysis of the results revealed an association of asthma phenotype and MHC class II type. Apart from the gene(s) in the MHC several other genes seem to be involved in the control of guinea pig asthma.

Topics: Anaphylaxis; Animals; Antibodies; Asthma; Genes, MHC Class II; Guinea Pigs; Histocompatibility Antigens Class II; Hybridization, Genetic; Major Histocompatibility Complex; Ovalbumin

Under in vitro circumstances, ovalbumin, administered serosally, caused a definite acid secretory response in the isolated whole stomach of sensitized mice. Acid secretion induced by challenge was inhibited by cimetidine or by pretreatment with disodium cromoglycate. It remained, however, unchanged by mepyramine or atropine. It is likely that a local histamine release caused by an anaphylactic reaction of type I might be involved in the pathogenesis of certain kinds of digestive diseases, i.e. peptic ulcer.

Topics: Anaphylaxis; Animals; Calcium; Cromolyn Sodium; Gastric Acid; Gastric Mucosa; Histamine; In Vitro Techniques; Mice; Ovalbumin; Stomach Ulcer

The heterophils in circulating blood and bone marrow were investigated in sensitized guinea pigs after acute anaphylactic shock (AAS) induced by inhalatory antigen challenge. Using histochemical, ultrastructural and in vitro methods evidence was obtained of a granule discharge from bone marrow reserve heterophils (BMRH). The mean number of primary (Biebrich scarlet positive) granules in BMRH decreased from 91 +/- 23 in the control to 74 +/- 23 after AAS. After AAS about 40% of BMRH and numerous circulating heterophils exhibited in the cytoplasm lucent areas which were surrounded by aggregates of granules. Only about 33% of BMRH were not affected by AAS. The rest of the cells showed different stages of granule aggregation and the lucent areas in the cytoplasm. Bone marrow basophils exhibited an early stage of degranulation. Almost 5% of BMRH ingested basophilic granules after AAS. Neither mortality rates in cytotoxicity tests nor antigen binding capacity were different in the experimental and control groups. It is suggested that the heterophils have a regulatory function during the anaphylactic reaction.

Topics: Anaphylaxis; Animals; Antigens; Bone Marrow; Cell Survival; Cytoplasmic Granules; Endocytosis; Granulocytes; Guinea Pigs; Male; Microscopy, Electron; Ovalbumin

125I-labelled ovalbumin (OVA) antigen did not sensitize guinea-pigs and anaphylaxis did not develop after native OVA challenge. The radiolabelled antigen was fixed by lymphocytes with highly specific receptors for 125I-OVA and this condition produced a continuous radiation damage leading to inactivation of the cells. As the proliferative response of lymphocytes did not occur, no antibody production was detected. This was demonstrated by passive haemagglutination techniques. However, the immune response to a simultaneously given non-radioactive antigen remained intact. It is supposed that radiation damage depended on specific activity of antigen destroying the antigen-specific lymphocyte clone selectively. The mechanism and the practical importance of the in vivo 'antigen suicide' is discussed.

Topics: Anaphylaxis; Animals; Antibody Formation; Clone Cells; Guinea Pigs; Half-Life; Immunization, Secondary; Immunoglobulin G; Iodine Radioisotopes; Lymphocytes; Ovalbumin

Antigens derived from Trichinella spiralis were used to challenge, in vitro, sensitized jejunum from infected guinea-pigs while monitoring ion transport properties of the tissue. Antigen challenge resulted in dose-dependent increases in trans-epithelial electrical potential difference and short circuit current. Both antigen-stimulated electrical alterations and Schultz-Dale contractions were demonstrated in small intestinal tissue after the passive transfer of immune serum containing anti-trichinella homocytotropic antibodies.

Topics: Anaphylaxis; Animals; Antigens, Helminth; Dose-Response Relationship, Immunologic; Electric Conductivity; Guinea Pigs; Hypersensitivity, Immediate; Immune Sera; Immunization, Passive; Intestinal Mucosa; Intestine, Small; Male; Membrane Potentials; Ovalbumin; Passive Cutaneous Anaphylaxis; Trichinellosis

This study was designed to determine the effects of different calcium concentrations on the perfused isolated guinea-pig heart preparation subjected to cardiac anaphylaxis. Following challenge both physiological and biochemical effects were determined on hearts from guinea-pigs previously sensitized to ovalbumin. Perfusion media containing either 1,2.54 or 5 mM of calcium was used. In comparison to nonsensitized controls challenged to ovalbumin, challenged sensitized hearts (CSH) perfused with 1 mM Ca2+ showed an initial increase in dF/dt, a prolonged rise in H.R. and depressed coronary flow. Raising the calcium concentration to either 2.54 or 5 mM in CSH preparations resulted in a marked increase in the release of lactate dehydrogenase (LDH) into the coronary effluent and depressed coronary flow. Perfusing CSH preparations with increasingly higher calcium concentrations more often produced severe tachyarrhythmias and fibrillation. The highest level of histamine released into the coronary effluent occurred immediately following challenge and then declined exponentially over the next 20 min. Both challenge and the administration of histamine induced an immediate but transient increase in H.R., a rise in dF/dt, and LDH release. The infusion of histamine produced an increase in coronary flow, but on porcine tubular coronary arterial segments only a direct constricting effect was obtained. The prior administration of cimetidine (10(-5) M) attenuated the rise in LDH and dF/dt in CSH and nonsensitized preparations infused with histamine (3 micrograms). However, although cimetidine did not affect the decreased coronary flow in CSH preparations, it initially attenuated the rise in coronary flow in preparations infused with histamine. These results suggest that calcium enhances the likelihood of tachyarrhythmias in cardiac anaphylaxis. The release of LDH in histamine-infused preparations and those CSH preparations perfused with 2.54 and 5 mM calcium-containing media also suggests the possibility that calcium enhances the damaging effects on the myocardial cell in cardiac anaphylaxis.

Topics: Anaphylaxis; Animals; Arrhythmias, Cardiac; Calcium; Cardiovascular Diseases; Cimetidine; Coronary Circulation; Female; Guinea Pigs; Heart; Heart Rate; Histamine; In Vitro Techniques; Kinetics; L-Lactate Dehydrogenase; Male; Myocardial Contraction; Ovalbumin; Perfusion

Intestinal absorption of various drugs was examined by means of in situ recirculation technique during local anaphylaxis. The antibody was determined by passive cutaneous anaphylaxis technique in rats immunized once or three times. The optimal condition of local anaphylaxis was determined by the leakage of Evans Blue. The most significant increase in leaks of the dye was observed by the intraluminal challenge with 400 mg of ovalbumin for 10 min in ovalbumin-immunized rats, and this condition was chosen as the optimal condition of local anaphylaxis. Under this condition, intestinal absorption of caffeine, phenylbutazone, and bromthymol blue (BTB) significantly decreased in ovalbumin-immunized rats compared with the control, whereas no significant effect was noted in the intestinal absorption of salicylic acid, quinine, pralidoxime iodide (2-PAM), tetracycline, and phenol red. In normal rats, no significant decrease was obtained in the intestinal absorption of caffeine, phenylbutazone, and BTB. On the other hand, the decreased absorption of BTB was not found in ovalbumin-immunized rats by the intraluminal challenge with bovine gamma-globulin. Furthermore, there was no significant change in the decreased absorption of BTB between rats immunized once and three times. The most effective condition for decreased BTB absorption was observed by the intraluminal challenge with 200 mg of ovalbumin for 10 min in ovalbumin-immunized rats, which almost correlated with the data of Evans Blue leakage. From these observations, it appears that the mucosal immune responses affect the intestinal absorption of low molecular weight drugs.

Topics: Anaphylaxis; Animals; Digestive System; Digestive System Physiological Phenomena; Immunization; Intestinal Absorption; Male; Molecular Weight; Ovalbumin; Passive Cutaneous Anaphylaxis; Pharmaceutical Preparations; Rats; Rats, Inbred Strains

Rats were intraperitoneally immunized with ovalbumin (egg albumin) with incomplete Freund's adjuvant, and the effect of intravenous challenge with ovalbumin on the intestinal blood flow was measured by means of hydrogen clearance method. The intestinal blood flow was significantly reduced by the antigen challenge in ovalbumin-immunized rats compared to the non-immunized rats. However, no significant change was observed on the intestinal blood flow in rats without challenge of the antigen. Moreover, the blood flow reduction was not found in ovalbumin-immunized rats challenged with bovine gamma-globulin. The effect was maintained for at least 16 weeks after the third immunization, but the reduced blood flow was gradually restored to the control level. The decrease in both blood flow and absorption of salicylic acid was recovered by nearly 70% of the control level when high dose of theophylline or caffeine was administered intravenously. In the case of gastric absorption during systemic anaphylaxis, similar results were also obtained by means of in situ loop technique. The decreased absorption of salicylic acid from the rat stomach also correlate with the reduced gastric blood flow. These findings suggest that the decreased absorption of salicylic acid from the gastrointestinal tract might be affected by the reduced blood flow during systemic anaphylaxis.

Topics: Anaphylaxis; Animals; Cattle; gamma-Globulins; Immunity; Intestinal Absorption; Intestines; Male; Ovalbumin; Pharmaceutical Preparations; Rats; Rats, Inbred Strains; Regional Blood Flow; Salicylates; Salicylic Acid; Stomach; Time Factors

Rats were immunized by intraperitoneal injection of ovalbumin (egg albumin) emulsified in Freund's incomplete adjuvant, and then the effect of an intravenous challenge with ovalbumin on salicylic acid absorption from the small intestine was examined by means of an in situ recirculation technique. The disappearance of salicylic acid from the luminal solution was significantly decreased in rats treated with ovalbumin compared with control groups treated with saline. The decreased absorption of salicylic acid in ovalbumin-immunized rats was related to the anti-ovalbumin antibody responses examined by passive cutaneous anaphylactic reactions. On the other hand, the decreased absorption of salicylic acid was not found in ovalbumin-immunized rats challenged intravenously with bovine gamma-globulin. Similar results were also noted in rats immunized via the footpads with ovalbumin. However, no significant change was observed in the intestinal absorption of salicylic acid in normal (nonimmunized) rats challenged intravenously with ovalbumin. Furthermore, intestinal absorption of sulfadimethoxine and sulfanilamide was significantly decreased during systemic anaphylaxis, whereas no change was observed in the absorption of sulfisoxazole, quinine, sulfanilic acid, and phenolsulfonphthalein. This suggests that the intestinal absorption of rapidly absorbed drugs, including salicylic acid, is more sensitive to systemic anaphylaxis than that of poorly absorbed drugs.

Topics: Anaphylaxis; Animals; gamma-Globulins; Injections, Intravenous; Intestinal Absorption; Male; Ovalbumin; Passive Cutaneous Anaphylaxis; Rats; Rats, Inbred Strains; Salicylates; Salicylic Acid

Guinea-pigs were sensitized to ovalbumin (OA) by immunization regimens chosen to cause antigen-induced bronchial anaphylactic responses mediated mainly either by IgE-like antibodies or by IgG1-like antibodies. Treatment of the IgE-producing animals for three weeks with the histamine H2-receptor antagonist cimetidine (1 mg kg-1 i.p. once a day) or with the H2-agonist dimaprit (0.1, 1.0, or 10 mg kg-1 i.p. once a day) led to a significantly reduced bronchial response capacity compared with that of the saline-treated controls challenged intravenously with antigen one week after the end of treatment. The changes were biphasic and not strictly dose-dependent. In contrast, acute treatment of immunized animals with a single dose of cimetidine (10 or 30 mg kg-1 i.v.) or dimaprit (1 or 10 mg kg-1 i.v.) 2 min before challenge with OA did not significantly affect the bronchial anaphylactic response. However, long-term treatment with cimetidine (10 mg kg-1) or the dimaprit analogue, S-[4-(N, N-dimethylamino)-butyl] isothiourea (SKF Compound 91488) (1 mg kg-1), which is reported not to activate H2-receptors, had no effect on the response capacity. Treatment with cimetidine (1 mg kg-1) or dimaprit (1 mg kg-1) did not influence the response capacity to antigen challenge in IgG1- type animals. Dimaprit (1 mg kg-1) did not affect the responsiveness to intravenous provocation with histamine in 'IgE-type' animals. Antigen-induced release of histamine from chopped lung tissue in vitro was not significantly affected in 'IgE-type' animals treated with cimetidine (1 mg kg-1) or dimaprit (1 mg kg-1). Treatment of immunized animals with cimetidine or dimaprit one week before and one week after a booster injection of antigen also led to reduced response capacity compared with that of saline-treated controls. However, the serum levels of IgE-like homocytotropic antibodies of these animals were not reduced; on the contrary, those of IgG1-antibody were increased in dimaprit-treated animals. These data show that intermittent treatment with histamine H2-agents reduces reagin-mediated anaphylactic response capacity in vivo in actively sensitized guinea-pigs by an as yet undefined mode of action.

Topics: Anaphylaxis; Animals; Bronchi; Cimetidine; Dimaprit; Female; Guinea Pigs; Histamine H2 Antagonists; Histamine Release; Immunoglobulin E; Immunoglobulin G; In Vitro Techniques; Lung; Male; Ovalbumin; Passive Cutaneous Anaphylaxis; Respiratory Function Tests; Thiourea

The nature of the beta-adrenoceptor population(s) mediating direct smooth muscle relaxation, inhibition of antigen-induced histamine release and inhibition of antigen-induced (leukotriene-mediated) smooth muscle contraction of human and guinea pig central and peripheral airways was investigated. Preferential blockade by beta 1- and beta 2-selective antagonists of the relaxation induced by beta 1- and beta 2-selective agonists, respectively, revealed the guinea pig tracheal smooth muscle relaxation to be mediated by both beta 1- and beta 2-adrenoceptors. Using a highly beta 2-selective antagonist, the NE-induced relaxation was split up biphasically into a beta 1- and a beta 2-component. In contrast, no such differential blockade was observed with the relaxation of the guinea pig lung parenchyma strip, neither with the human tracheal, main bronchus and respiratory bronchiolus smooth muscle, which are all mediated by homogeneous beta 2-adrenoceptor populations. Only in the guinea pig trachea did neuronal and extraneuronal uptake inhibitors produce pronounced left shifts of the NE- and ISO-induced relaxation curves, respectively, suggesting a causal relationship between noradrenergic innervation and the presence of the beta 1-adrenoceptor subpopulation in the airways. Using the same techniques, it was established that inhibition of antigen-induced histamine release from guinea pig lung and tracheal mast cells is mediated by homogeneous beta 2-adrenoceptor populations as well. In contrast to catecholamines, non-catecholamine beta-agonists such as fenoterol, clenbuterol and zinterol had a substantially higher apparent affinity for the inhibition of the anaphylactic (leukotriene-mediated) guinea pig tracheal contraction than for the inhibition of histamine release; the same was true for lung tissue, though the difference was less pronounced. With some non-catecholamine beta-agonists considerable selectivity both in central and peripheral airway preparations was observed for the inhibition of anaphylactic contraction as compared with smooth muscle relaxation.

Topics: Anaphylaxis; Animals; Bronchi; Corticosterone; Guinea Pigs; Histamine Release; Humans; Immunization; Isoproterenol; Male; Methacholine Chloride; Methacholine Compounds; Muscle Contraction; Muscle Relaxation; Muscle, Smooth; Norepinephrine; Ovalbumin; Phenoxybenzamine; Practolol; Receptors, Adrenergic; Receptors, Neurotransmitter; Trachea

Investigations into the role of allergic enteropathy in acute and chronic intestinal inflammation have been hampered by the lack of objective confirmation for intestinal mast cell activation. Utilizing an established model of acute allergic enteropathy in the rat, we report the enhanced intraluminal recovery of the mast cell mediator histamine after in vivo antigen challenge in sensitized animals. The enhanced histamine recovery is dose dependent, antigen-specific, and restricted to that segment of bowel challenged, thus confirming local intestinal anaphylaxis. The progression of histologic enteropathy is documented and shown to correlate with the entry of mast cells into the intestinal lumen during, but not before, the anaphylactic response. Pretreatment of the sensitized animal with prostaglandin E2 or doxantrazole, but not cromolyn, significantly inhibits the anaphylactic response.

Topics: Acute Disease; Adjuvants, Immunologic; Anaphylaxis; Animals; Dinoprostone; Enteritis; Female; Histamine; Histamine Release; History, Ancient; Hookworm Infections; Immunization; Nippostrongylus; Ovalbumin; Prostaglandins E; Rats; Rats, Inbred Strains; Thioxanthenes; Xanthones

Desmodium adscendens, used by herbalists in Ghana for the treatment of asthma, is anti-anaphylactic in vitro. As the plant material is administered orally, in vivo studies of its anti-anaphylactic property were undertaken using the guinea-pig. The results show that both aqueous and ethanolic extracts of D. adscendens, when taken orally, reduce anaphylactic contractions, interfere with histamine-induced contractions, and reduce the amount of smooth muscle stimulating substances released from lung tissue of guinea pigs.

Topics: Anaphylaxis; Animals; Guinea Pigs; Histamine; Ileum; In Vitro Techniques; Lung; Muscle Contraction; Muscle, Smooth; Ovalbumin; Plant Extracts

Previous studies have demonstrated the decrease of intestinal salicylic acid absorption in ovalbumin-immunized rats during systemic anaphylaxis. In the present study, the mechanism whereby systemic anaphylaxis interferes with the intestinal absorption of salicylic acid was studied. The pH of the luminal solution was not affected by the intravenous challenge with ovalbumin. A significant increase of the intraluminal protein was observed in rats under systemic anaphylaxis. However, there was no significant difference between ovalbumin-treated rats and saline-treated ones on the binding of salicylic acid with intraluminal macromolecular substances. Enhanced mucus release in the perfusate was also observed in sensitized rats but the extent of decrease in absorption of salicylic acid did not correlate with the increase in amount of the intraluminal mucus in the same animals. In addition, no significant effect was observed on the uptake by the intestinal everted sac of rats with systemic anaphylaxis. These findings suggested that mucus as well as protein is not responsible for the decrease of absorption of salicylic acid induced by systemic anaphylaxis. From these observations, it would appear that the circulatory changes in the gastrointestinal tract may play an important role in the decreased absorption of salicylic acid during systemic anaphylaxis.

Topics: Anaphylaxis; Animals; Evans Blue; Immunity; Intestinal Absorption; Male; Mucus; Ovalbumin; Permeability; Pharmaceutical Preparations; Protein Binding; Proteins; Rats; Rats, Inbred Strains; Salicylates; Salicylic Acid

Mice sensitized with two intraperitoneal injections of ovalbumin and challenged intranasally with the same antigen developed a non-fatal anaphylactic shock peaking in severity 30 min after challenge. Increases in haematocrit were noted which corresponded to the severity of signs of shock displayed by mice. Severity of shock also correlated with IgE and IgG levels. Sensitization by the nasal route, and use of B. pertussis vaccine as adjuvant had no qualitative effect upon the response. Cobra venom factor depletion of C3 in vivo did not alter the response of mice, which suggests anaphylaxis did not involve complement activation. Sensitivity was not transferrable to non-immune mice with serum. Passive sensitization with polyclonal and monoclonal antibodies produced inconsistent results. Possible mechanisms of anaphylaxis are discussed.

Topics: Administration, Intranasal; Anaphylaxis; Animals; Antigens; Complement C3; Female; Hematocrit; Immunization, Passive; Immunoglobulins; Injections, Intraperitoneal; Male; Mice; Mice, Inbred Strains; Ovalbumin; Pertussis Vaccine

The i.p. injection of 1 microgram of TM3-OA or TM9-OA with 1 mg of A1(OH)3 into B6D2F1 mice elicited the production of antibodies of the IgE and other classes to the trimellityl (TM) group and ovalbumin (OA). The induction of anti-TM antibodies belonging to the IgE and other immunoglobulin classes was specifically suppressed by the administration of tolerogenic conjugates prepared by coupling trimellitic anhydride (TMA) to the hydrophilic non-immunogenic polymer, polyvinyl alcohol (PVA), prior to immunization with TM-OA conjugates. More importantly, established anti-TM responses were also suppressed by these TM-PVA conjugates. By contrast, however, treatment with TM-PVA conjugates did not affect either the primary or the established anti-OA antibody response. The tolerogenic effects of the PVA conjugates were dose-dependent and appeared also to be dependent on the epitope density. Treatment with these conjugates also prevented immunized mice from showing any symptoms of systemic anaphylaxis on challenge with polyvalent TM-protein conjugates. These findings indicate that these conjugates may have the potential of useful therapeutic agents for the treatment of TMA-induced pulmonary hypersensitivity diseases.

Topics: Anaphylaxis; Animals; Antibody Formation; Dose-Response Relationship, Immunologic; Female; Immune Tolerance; Immunoglobulin E; Mice; Ovalbumin; Passive Cutaneous Anaphylaxis; Phthalic Acids; Phthalic Anhydrides; Polyvinyl Alcohol

Guinea-pigs were sensitized either by i.p. administration or by a novel procedure involving inhalation of ovalbumin (2, 0.2 and 0.002%) on days 0, 5 and 19 respectively. Lung strips from these guinea-pigs were challenged with both low (0.02 micrograms/ml) and high (10 micrograms/ml) concentrations of ovalbumin and the responses compared. Whereas the low level antigen gave consistent contractions following aerosol sensitization, no response was observed from the i.p. sensitized guinea-pig lung strips. Marked differences were also observed following the high ovalbumin challenge, where the aerosol sensitized lungs gave almost twice the response as tissue from the i.p. sensitized guinea-pigs, the former being approximately 140% of that observed with acetyl-beta-methyl choline (1 mM). Furthermore, the response elicited in the lungs from aerosol sensitized guinea-pigs were not modified by the addition of high concentrations of the H1-antagonist diphenhydramine (100 microM), before or subsequent to challenge. The data suggest that the aerosol sensitization procedure gives rise to a contractile response in guinea-pig lung strips which contains no observable histamine component.

Topics: Anaphylaxis; Animals; Antigens; Diphenhydramine; Female; Guinea Pigs; Histamine; In Vitro Techniques; Lung; Muscle Contraction; Ovalbumin

PVG rats given injections of 1 microgram ovalbumin (OA) together with 10 mg Silica gel failed to provide serosal mast cells or lung tissue with the capacity to release histamine on in vitro challenge with the antigen. However, if such animals were injected i.p. with 100 mg of alum (without any further antigen addition) 3-9 weeks after the primary antigen injection, their mast cells and lung tissue showed a clear-cut capacity to respond in vitro, when examined 1 week after the alum injection. Injection of only 15 mg alum did not induce such a response capacity. The fading of the reactivity induced by an alum injection could be prevented by a repeated injection of the adjuvant alone. Pretreatment of the rats with cyclophosphamide (33 mg/kg) 2 days before the primary antigen injection did not affect the response capacity induced by a booster injection 3 weeks later. S.c. injection of alum also precipitated response capacity in animals primed by i.p. injection of antigen and Silica gel. The anaphylactic response capacity induced by injection(s) of alum was generally accompanied by increased levels of OA-IgE and especially OA-IgG2a antibody; however, a clear-cut correlation between either serosal mast cell or lung tissue response capacity and serum OA-IgE or IgG2a antibody titer could not be demonstrated. These data show that in primed animals, which do not express allergic response capacity, such a capacity can be induced by injecting adjuvant alone, even several weeks after the primary antigen injection.

Topics: Aluminum Hydroxide; Anaphylaxis; Animals; Cyclophosphamide; Dose-Response Relationship, Immunologic; Histamine Release; Immunization; Immunization, Passive; Immunoglobulin E; Immunoglobulin G; Ovalbumin; Rats; Rats, Inbred Strains; Respiratory Hypersensitivity

The F1 generation, produced by mating Wistar rats from the Tuck colony which react to dextran (R rats) with Wistar rats from the NELP colony which do not react (NR rats) all responded to dextran with an anaphylactoid oedema reaction, and developed arthritis after adjuvant injections (AIA), but failed to show ovalbumin-induced delayed hypersensitivity reactions (OA) and experimental allergic encephalomyelitis (EAE). Back-crossing the F1 generation with NR rats produced animals, only half of which responded to dextran, though all the offspring reacted well to AIA, but poorly to OA and EAE. This confirms that resistance to AIA is not associated with resistance to dextran.

Topics: Adjuvants, Immunologic; Anaphylaxis; Animals; Arthritis, Experimental; Arthus Reaction; Dextrans; Hypersensitivity, Delayed; Mycobacterium tuberculosis; Ovalbumin; Rats

In an attempt to elucidate the pathophysiological mechanisms of gastric anaphylactic ulcer we measured tritiated thymidine incorporation in gastric cells, their mitotic rate and the degranulation of mast cells in the preulcerous phase. The results showed that there is a highly significant increase in cell turnover and mast cell degranulation in the mucosa of sensitized animals. Changes were found at the site of ovalbumin challenge, where point ulceration occurred within 48-72 h. The tissue culture studies demonstrated that the mucosa of sensitized animals produces significantly more histamine when challenged with ovalbumin than the mucosa of nonsensitized animals. Addition of histamine to the tissue culture medium in which normal gastric mucosa was cultured led to an increase in [3H]-thymidine uptake at low concentration, and a decrease at high concentration. Serotonin added to the culture medium had no significant effect on [3H]-thymidine uptake, but heparin at high concentration was found to have a stimulatory effect. These studies show that anaphylactic gastric ulceration is associated with an increase in mucosal cell turnover, and that the mast cell mediator responsible for this increase may be histamine.

Topics: Anaphylaxis; Animals; Cells, Cultured; Disease Models, Animal; Heparin; Histamine; Histamine Release; In Vitro Techniques; Intestinal Mucosa; Mast Cells; Mitosis; Muridae; Ovalbumin; Serotonin; Stomach; Stomach Ulcer

Two strains of guinea-pigs selectively bred for either high (IMM/S) or low (IMM/R) responsiveness to ovalbumin-induced respiratory anaphylaxis were examined for genetic homogenicity by skin transplantation experiments and screened for polymorphism of erythrocyte enzymes (alkaline phosphatase, carbonic anhydrase, esterase D, and phosphoglucomutase). According to the transplantation data it can be concluded that the brother x sister matings have resulted in lines of guinea-pigs with a high degree of genetic homogenicity. The results from the typing of polymorphic enzymes showed that only phosphoglucomutase exhibited different allelic forms among the tested animals, but no correlation was found between this polymorphism and responsiveness to ovalbumin.

Topics: Anaphylaxis; Animals; Erythrocytes; Female; Graft Rejection; Guinea Pigs; Histocompatibility; Isoenzymes; Male; Ovalbumin; Phosphoglucomutase; Skin Transplantation; Transplantation, Homologous

SD rats were sensitized by an i.p. injection of 1 microgram or 10 micrograms ovalbumin (OA) together with 10 mg Silica gel. At the indicated time after sensitization, allergic response capacity of the animals was estimated by measuring changes in intratracheal pressure induced by an i.v. injection of 0.3 mg OA (low challenge dose) or 5 mg OA (high challenge dose). Animals given 1 microgram OA in Silica gel showed no response capacity at 14, 35 or 47-48 days after sensitization. Animals injected with 10 micrograms OA showed a clear-cut response with a peak at 14 days; at 7 weeks after immunization the response capacity had faded almost completely. Specific OA-IgE antibody and total IgE serum levels were examined by radioimmunoassay. A slight increase in OA-IgE antibody was recorded in animals injected 14 days before test with 10 micrograms ovalbumin and Silica gel; animals given 1 microgram OA and Silica showed no OA-IgE antibody. Five weeks after sensitization, some animals of each group were injected i.p. with 100 mg alum, B. pertussis vaccine (2 ml of Perthydral), or saline, all injections being made without any further antigen addition. 12-13 days after such an injection, alum-treated animals showed high response capacity at bronchial anaphylactic tests and high OA-IgE antibody levels but comparably low levels of total IgE. Animals injected with B. pertussis, on the other hand, showed low response capacity (bronchial anaphylactic tests and OA-IgE antibody levels) but high total IgE-antibody levels. The bronchial anaphylactic response in the B. pertussis-injected animals but not the alum-injected animals was significantly correlated to serum IgG2a antibody levels. These results show that injection of alum or B. pertussis vaccine without antigen can precipitate/enhance anaphylactic response capacity and production of specific and non-specific IgE and IgG2a.

Topics: Adjuvants, Immunologic; Aluminum Hydroxide; Anaphylaxis; Animals; Dose-Response Relationship, Immunologic; Immunization, Secondary; Immunoglobulin E; Immunoglobulin G; Male; Ovalbumin; Pertussis Vaccine; Rats; Rats, Inbred Strains; Respiratory Hypersensitivity; Silica Gel; Silicon Dioxide

A direct comparison of the role of leukotrienes in mediating the increase in microvascular permeability associated with guinea pig tracheal and cutaneous anaphylaxis was obtained by simultaneous administration of inflammatory stimuli to both trachea and ear. The SRS-A antagonist, FPL 55712, reduced the increase in tracheal extravascular albumin content evoked by LTC4, LTD4, and LTE4 but failed to significantly reduce the tracheal microvascular permeability response associated with local anaphylaxis. Moreover, the inhibitory effect of the histamine H1-receptor antagonist, mepyramine, was not augmented by the additional presence of FPL 55712. In contrast to tracheal anaphylaxis, a distinct leukotriene component was indicated in cutaneous anaphylaxis since the mepyramine-FPL 55712 combination produced a greater inhibition than mepyramine alone. These results suggest that the degree of leukotriene involvement in anaphylaxis may vary between tissues.

Topics: Anaphylaxis; Animals; Capillary Permeability; Chromium Radioisotopes; Chromones; Female; Guinea Pigs; Histamine; In Vitro Techniques; Leukotriene E4; Ovalbumin; Passive Cutaneous Anaphylaxis; Pyrilamine; SRS-A; Time Factors; Trachea

Studies on antigenicity of suloctidil were performed on ASA, Schultz-Dale reaction, PCA and PHA in guinea pigs. Two sensitizing procedures were enforced. One was performed by means of treatment of suloctidil (p. o. and i. p.) and the other was done by means of injection of suloctidil, suloctidil-BSA-mixture and suloctidil-BSA-conjugate emulsified with FCA. Guinea pigs treated with suloctidil by oral or intraperitoneal administration showed no ASA, Schultz-Dale reaction, PCA and PHA by the challenge of suloctidil. The animals treated with suloctidil-BSA-conjugate only evoked severe anaphylactic reaction to challenge of suloctidil-OVA-conjugate. Guinea pigs treated with suloctidil and suloctidil-BSA-mixture showed no anaphylactic reaction to challenge of suloctidil, suloctidil-OVA-mixture and suloctidil-OVA-conjugate. The animals sensitized with suloctidil-BSA-conjugate showed no anaphylactic reaction to challenge of suloctidil and suloctidil-OVA-mixture. Therefore, it is concluded that suloctidil does not have any antigenicity.

Topics: Anaphylaxis; Animals; Antigens; Freund's Adjuvant; Guinea Pigs; Hemagglutination Tests; Ileum; Immunization; In Vitro Techniques; Male; Ovalbumin; Passive Cutaneous Anaphylaxis; Propanolamines; Protein Binding; Serum Albumin, Bovine; Suloctidil

Topics: Anaphylaxis; Animals; Blood Pressure; Endorphins; Guinea Pigs; Male; Naloxone; Ovalbumin; SRS-A; Thyrotropin-Releasing Hormone; Time Factors

Antihistamine-resistant anaphylactic bronchospasm in guinea pigs is increased with increasing doses of antigen (ovalbumin, OA) challenge. This was observed in passively and actively sensitized animals, and by both i.v. and aerosol routes of antigen challenge. At a challenge concentration of 100 mg/kg OA, antihistamines were virtually inactive. Indeed, the resulting bronchospasm was inhibited by isoproterenol, theophylline and ketotifen but not any anticholinergics, anti-5HT, SRS-A antagonists, arachidonic acid lipoxygenase inhibitors or antiallergic drugs. However, in the presence of chlorpheniramine, the response was antagonized by SRS-A antagonists (FPL 55712 and isamoxole), but not the lipoxygenase inhibitors (BW 755C, ETYA, NDGA and phenidone). This suggests that the antihistamine-resistant bronchospasm produced in guinea pigs challenged with high antigen concentrations might be the result of SRS-A release. This is by no means certain since the currently available SRS-A antagonists possess other mechanisms of action; furthermore, the failure of lipoxygenase inhibitors to influence this response is not consistent with a role for SRS-A. Elucidation of the mechanism of the antihistamine-resistant bronchospasm awaits development of more specific SRS-A antagonists.

Topics: Aerosols; Anaphylaxis; Animals; Bronchial Spasm; Chlorpheniramine; Chromones; Guinea Pigs; Immunization, Passive; Lipoxygenase Inhibitors; Male; Ovalbumin; SRS-A

In a study of ocular tissues undergoing anaphylaxis, in uninjected rats most mast cells contained electron-dense granules with no discernible internal structure. A few cells showed varying degrees of swelling of the matrix granules. In rats injected with normal rabbit serum, more mast cells showed swelling of the granule matrix and a few showed extensive swelling of nearly all granules. Mast cells from rats undergoing anaphylaxis by either anti-IgE or antigen injection showed membrane and granule alterations: extensive dendritic processes, fusion of granule membranes, fusion between granule and plasma membranes, and disruption of plasma membranes. Communication was established between the exterior of the cell and contents of individual granules of cisternae formed by several fused granules. The matrix of nearly all granules was extensively swollen.

Topics: Anaphylaxis; Animals; Eye; Immune Sera; Mast Cells; Ovalbumin; Rabbits; Rats; Rats, Inbred Strains

Two strains of guinea-pigs selectively bred for either high (IMM/S) or low (IMM/R) ovalbumin-induced respiratory anaphylaxis were examined for correlations between respiratory anaphylaxis and production of homocytotropic and passive hemagglutinating antibodies. The passive cutaneous anaphylaxis assay (PCA-assay) was used to test for the production of the three classes of homocytotropic antibodies, IgGla, IgGlb and IgE after immunization either by inhalation of the antigen or by intraperitoneal injection of the antigen adsorbed on aluminium hydroxide. IgE was not detected in any of the strains within the seven-week period following immunization. When immunization was performed by the inhalation technique, antibodies of the two subclasses IgGla and IgGlb as well as hemagglutinating antibodies were demonstrated in all sublines from IMM/S, while in sublines from IMM/R IgGla and IgGlb were never found, and hemagglutinating antibodies were only detected in small amounts or not at all. However, injection of the antigen with aluminium hydroxide as adjuvant resulted in production of hemagglutinating antibodies as well as IgGla and IgGlb in both IMM/S and IMM/R. When such animals were challenged by inhalation of the antigen, a severe respiratory anaphylactic response was induced in guinea-pigs from IMM/S only.

Topics: Adjuvants, Immunologic; Aluminum Hydroxide; Anaphylaxis; Animals; Antibodies; Disease Susceptibility; Guinea Pigs; Hemagglutination Tests; Hemagglutinins; Immunization Schedule; Immunoglobulin G; Ovalbumin; Passive Cutaneous Anaphylaxis; Reagins

We evaluated two children with allergy to egg-white protein (ovalbumin) who had generalized urticaria, angioedema, and respiratory difficulty after immunization with live rubeola vaccine. In both patients, serum IgE reactive with ovalbumin-related antigens in the vaccine was demonstrated. Subsequent evaluation of 24 children with ovalbumin allergy revealed that those who had positive ovalbumin skin tests, but no clinical reaction to egg white, were skin test negative on prick and intradermal testing with measles vaccine and were safely immunized. They had no detectable IgE directed against the rubeola vaccine, although IgE directed at ovalbumin was present. Six patients who had severe allergic hypersensitivity reactions on exposure to ovalbumin had IgE antimeasles vaccine antibody and had positive reactions after intracutaneous or intradermal testing with the vaccine. These patients were safely immunized with increasing volumes (0.05 ml increments every 20 minutes) of measles vaccine to receive the full dose. These studies suggest that children with severe allergic hypersensitivity to egg white should be screened with an intracutaneous test prior to immunization with measles vaccine; however, children who have positive skin tests but no clinical reaction to ovalbumin exposure are at minimal risk for hypersensitivity reactions to measles immunization, as previously reported.

Topics: Anaphylaxis; Cross Reactions; Egg Proteins; Humans; Immunoassay; Immunoglobulin E; Infant; Male; Measles Vaccine; Ovalbumin; Skin Tests

Ocular anaphylaxis was produced in rats by the injection of egg albumin into ocular adnexal tissues of immunized animals. Mast cells in the tip of the eyelid from normal, antigen-injected control and antigen-injected immunized rats were examined at 1/2, 1, 6 and 24 hr. The number of cells and their morphology was determined. All three groups had the same number of mast cells at all time intervals. Extensive mast-cell degranulation was observed at 1/2 and 1 hr in lid tips of immunized, antigen-challenged rats. By 24 hr, the mast cells appeared to have 'healed' and regranulated, although it was possible to distinguish these cells from mast cells of normal animals. We conclude that under certain conditions, mast cells participating in ocular anaphylaxis are not destroyed but survive and regenerate granules within the first 24 hr.

Topics: Anaphylaxis; Animals; Cell Count; Cytoplasmic Granules; Eyelid Diseases; Eyelids; Mast Cells; Ovalbumin; Rats; Rats, Inbred Strains; Time Factors

Certain flavonoids inhibit antigen-induced release of histamine from mast cells and basophils and also inhibit contraction of guinea pig ileum induced by histamine, acetylcholine, and PGE2. We examined the effect of one flavonoid, quercetin, on anaphylactic smooth muscle contraction of ileum from guinea pigs sensitized to egg albumin. Quercetin inhibited both the phasic and tonic components of anaphylactic contraction in a concentration-dependent fashion (IC50 approximately 10 microM). Whether this is primarily an effect on mast cell mediator release or inhibition of mediator effects on smooth muscle has not been established.

Topics: Anaphylaxis; Animals; Flavonoids; Guinea Pigs; Ileum; Male; Muscle, Smooth; Ovalbumin; Quercetin

Topics: Anaphylaxis; Animals; Dogs; Hematocrit; Hemodynamics; Ovalbumin

Brown-Norway rats, sensitized with trinitrophenyl (TNP) haptenized ovalbumin and AIPO4 as adjuvant 12 days before, were challenged with trinitrophenyl haptenized bovine serum albumin intravenously, while lung function (Vt, V, Ppl, Fres, Cdyn, and Rl) and cardiovascular function (BP and Fheart) were measured continuously. This resulted in a highly reproducible, plasma IgE-antiTNP related, immediate anaphylactic response characterized by a short-lasting (8-10 min) bronchoconstriction, together with a long-lasting fall in blood pressure. All rats died in shock within 21-150 min. This method is simple and appeared to be highly reproducible and therefore suitable to screen or study antiallergic drugs in vivo.

Topics: Anaphylaxis; Animals; Bronchial Diseases; Cardiovascular Diseases; Disease Models, Animal; Female; Haptens; Immunoglobulin E; Male; Ovalbumin; Rats; Rats, Inbred BN; Serum Albumin, Bovine; Trinitrobenzenes

Topics: Anaphylaxis; Animals; Antigens; Barium; Barium Compounds; Chlorides; Female; Guinea Pigs; Histamine; Histamine H1 Antagonists; In Vitro Techniques; Methysergide; Metiamide; Ovalbumin; Papaverine; Phentolamine; Pulmonary Artery; Vasoconstriction

In isolated atria from sensitized guinea-pigs, antigenic challenge with ovalbumin induces an anaphylactic reaction in which there is an increased rate and force of contraction. At the same time, stimulation-induced release of [3H] noradrenaline is inhibited by 40%. Cimetidine decreased the tachycardia occurring during anaphylaxis but no effect on the inhibition of stimulation-induced transmitter release. It is known that antigenic challenge of sensitized guinea-pig atria release histamine from mast cells; this histamine acts postjunctionally to increase heart rate. However, the inhibition of noradrenergic transmitter release is not due to the stimulation of prejunctional inhibitory histamine receptors.

Topics: Anaphylaxis; Animals; Cimetidine; Female; Guinea Pigs; Heart; Heart Rate; In Vitro Techniques; Male; Nerve Endings; Norepinephrine; Ovalbumin; Receptors, Histamine; Sympathetic Nervous System

A new method has been developed to detect antigen-induced histamine release in the blood of allergic rats. This in vivo model of systemic anaphylaxis has been utilized to evaluate drugs for histamine release inhibition activity. Compounds were administered by various routes at appropriate times prior to or concomitant with antigen challenge. One minute after challenge the rats were bled into tubes containing heparin and aminoguanidine. Histamine concentrations were determined by a radioenzyme technique after separation of the plasma. Experiments demonstrated that: (a) rats passively sensitized with reaginic serum exhibited elevated blood histamine upon i.v. antigen challenge in a reproducible and dose-dependent manner; (b) heat-treatment of the reaginic serum abolishes antigen-induced histamine release; and (c) antigen-induced histamine release is inhibited by disodium cromoglycate, in a dose-dependent manner and it is also inhibited by isoproterenol or isobutyl-methylxanthine.

Topics: Anaphylaxis; Animals; Antigens; Binding Sites, Antibody; Cromolyn Sodium; Histamine; Histamine Release; Immunoglobulin E; Male; Ovalbumin; Rats; Rats, Inbred BN; Rats, Inbred Lew

Verapamil was found to be an effective inhibitor of isometric tension in in vitro, experimental anaphylaxis in guinea pig trachealis smooth muscle. The mean IC50 for protection studies was 2 X 10(-4) M; the drug was also effective as a bronchoreversal agent. The inhibitory effect of verapamil upon the initial rate of isometric muscle tension suggests an action beyond simple calcium channel inhibition. No inhibition of tracheal mast cell histamine release was observed. Verapamil was slightly more potent than theophylline in this in vitro anaphylactic model.

Topics: Anaphylaxis; Animals; Asthma; Calcium Channel Blockers; Depression, Chemical; Disease Models, Animal; Epitopes; Guinea Pigs; Histamine Release; Immunization, Passive; Male; Muscle Contraction; Muscle, Smooth; Ovalbumin; Theophylline; Trachea; Verapamil

The experiments were carried out on immunized guinea-pigs. Histamine concentration in the blood and the lung tissue, the plasma prekallikrein and kininogen levels, kininase and fibrinolytic activity were determined. The examinations were made before antigen challenge, during anaphylactic reaction and after pharmacological inhibition of proteolysis. As protease inhibitors--Trasylol and EACA were used. The inhibition of the kinin and fibrinolytic systems by Trasylol and EACA did not markedly affect the allergic symptoms and did not change the high level of blood and lung tissue histamine. These experiments suggest that activation of the kinin system is not essential for the initiation of the immediate response but is the consequence of immunological release of histamine and other mediators.

Topics: Anaphylaxis; Animals; Asthma; Fibrinolysis; Guinea Pigs; Histamine Release; In Vitro Techniques; Kallikreins; Kininogens; Kinins; Lung; Ovalbumin

In conscious guinea-pigs isoprenaline, adrenaline and salbutamol protected the animals against egg albumin and histamine microshock in a dose-dependent manner. Chronic aerosol pretreatment three times daily with adrenaline or isoprenaline, but not with salbutamol, enhanced the acute dose protection against egg albumin microshock, but there was no enhancement when the bronchodilators were given six times daily. Aminophylline when administered three times daily enhanced the protective effect of an acute dose of adrenaline. With histamine microshock, desensitization occurred to adrenaline, when given three and six times daily, and to isoprenaline, when given six times daily, but not to salbutamol. Cross-desensitization could be induced to adrenaline by isoprenaline but not by salbutamol. The data indicate that, depending on the experimental conditions, enhancement of or desensitization to the effects of bronchodilators could be shown in conscious guinea-pigs.

Topics: Aerosols; Anaphylaxis; Animals; Bronchodilator Agents; Desensitization, Immunologic; Guinea Pigs; Histamine; Male; Ovalbumin; Receptors, Adrenergic, beta

Comparisons were drawn between the effects of Nippostrongylus brasiliensis infestation upon IgE synthesis and the in vivo expression of allergic reactions to ovalbumin (OV) in weanling, juvenile and adult rats. Parameters examined included total and antigen (OV)-specific IgE levels in serum and the relationship between serum levels of antigen-specific IgE in individual parasitized rats and the magnitude of their subsequent reactions to intravenous or intradermal antigenic challenge. On the basis of parallel trials employing non-infested age-matched controls, parasitized adult and juvenile animals manifested allergic reactivity to the full potential of their individual specific antibody levels. In contrast, the magnitude of allergic reactions in parasitized weanlings was markedly depressed below that expected from their IgE antibody scores. The most notable additional feature distinguishing parasitized weanling rats from infested animals of other ages was the presence in their serum of extremely high levels of 'irrelevant' IgE.

Topics: Aging; Anaphylaxis; Animals; Female; Hypersensitivity, Immediate; Immunoglobulin E; Nematode Infections; Nippostrongylus; Ovalbumin; Passive Cutaneous Anaphylaxis; Radioallergosorbent Test; Rats; Skin Tests

Sprague Dawley rats were immunized with graded doses of ovalbumin (OA) together with alum. The capacity of the animals to produce a bronchial anaphylactic response to intravenous antigen challenge was related to serum OA-IgE and OA-IgG2a antibody levels estimated by radioimmunoassay. A significant correlation between bronchial anaphylactic response capacity and OA-IgE antibody levels was found under a few, but not all, of several carefully chosen experimental conditions. No correlation was demonstrable between the in vivo reactivity of the animals and their serum levels of OA-specific IgG2a antibodies.

Topics: Anaphylaxis; Animals; Antigens; Bronchial Spasm; Dose-Response Relationship, Immunologic; Immunoglobulin E; Immunoglobulin G; Male; Ovalbumin; Rats; Rats, Inbred Strains; Time Factors

Topics: Anaphylaxis; Animals; Guinea Pigs; Heart; Immunoglobulin G; Ovalbumin

The sensitizing activity to egg protein of an A1PO4-adjuvant purified and concentrated influenza-A vaccine was examined in animal experiments and in man. Intravenous injection of ovalbumin caused anaphylactic symptoms and/or fatal anaphylactic shock in prevaccinated guinea-pigs. Ovalbumin-specific antibodies detectable by the passive haemagglutination reaction (PHA) appeared in the blood serum of the vaccinated animals. Model experiments with purified ovalbumin suggested that 1 human dose of the vaccine contained egg protein in the range from 0.1 to 1 ng, and that the antigenic effect of the vaccine grew to more than 10(3)-fold by its adsorption to A1PO4 gel. Adults who in previous years had been immunized with similarly prepared influenza vaccine several times responded with mild reactions; symptoms suggestive of hyperergy did not occur, irrespective of the vaccination history. In the prevaccination serum sample of some vaccines, ovalbumin-specific PHA antibodies were found up to titres independent of the number of the previous immunizations. The concentration of the ovalbumin-specific antibodies of the IgE class was by several orders of magnitude lower in the postvaccination samples than in the serum of some patients hypersensitive to egg protein.

Topics: Adjuvants, Immunologic; Adolescent; Adult; Aged; Aluminum Compounds; Anaphylaxis; Animals; Chick Embryo; Child; Child, Preschool; Egg Proteins; Female; Guinea Pigs; Hemagglutinins; Humans; Immunoglobulin E; Infant; Influenza Vaccines; Male; Middle Aged; Ovalbumin; Phosphates

Topics: Anaphylaxis; Animals; Antibodies; Antigens; Chick Embryo; Drug Contamination; Guinea Pigs; Immunization; Influenza Vaccines; Ovalbumin; Time Factors; Vaccines, Attenuated

This investigation examines the effect of a booster dose and cyclophosphamide treatment in guinea pigs sensitized according to different sensitization regimens. The results show that guinea pigs sensitized with a high dose of ovalbumin (10 microgram) develop a transient bronchial reactivity. The administration of a booster dose to guinea pigs sensitized according to this regimen does not result in any secondary response. Cyclophosphamide 30 mg/kg given 2 days before the booster injection or the primary sensitization results in a marked increase in bronchial reactivity when challenged with ovalbumin. This increased bronchial reactivity is reflected in the IgE-like antibody titre examined by PCA. Guinea pigs primarily sensitized with a low dose of ovalbumin (0.5 microgram) show no bronchial reactivity when challenged with antigen. However, guinea pigs sensitized according to this regimen and given a booster dose show a marked secondary response when challenged 7 days after the booster injection. An examination of the antibody classes by PCA show that the booster injection causes an increase in the IgG1--and also in the IgE-like antibody production.

Topics: Aluminum Hydroxide; Anaphylaxis; Animals; Antigens; Bronchi; Cyclophosphamide; Dose-Response Relationship, Immunologic; Female; Guinea Pigs; Histamine Release; Immunization; Immunization, Secondary; Lung Compliance; Male; Ovalbumin; Passive Cutaneous Anaphylaxis

Bronchial anaphylactic reactions, estimated as increase in intratracheal pressure, were precipitated by intravenous injections of antigen into actively sensitized SD rats. The degree of bronchial reactivity was found to depend on both the challenge dose and the immunization dose of antigen; therefore the course of the capacity to respond was recorded as a function of these variables. The degree of the bronchial anaphylactic response could be reduced by pretreatment with disodium cromoglycate, terbutaline or a new anti-allergic xanthine derivative, D 4026, in some groups of animals. The efficacy of each agent was found to depend on the dose of antigen used for sensitization and for provocation of the bronchial reaction rather than on the strength of the response. Taken together, the data suggest that more than one type of homocytotropic antibody mediates bronchial anaphylactic reactivity in the SD rat.

Topics: Adjuvants, Immunologic; Aluminum Hydroxide; Anaphylaxis; Animals; Antigens; Bronchial Spasm; Cromolyn Sodium; Dose-Response Relationship, Immunologic; Immunization, Passive; Immunization, Secondary; Male; Methacholine Compounds; Ovalbumin; Pertussis Vaccine; Rats; Serotonin; Silicon Dioxide; Terbutaline; Theophylline; Time Factors

Topics: Anaphylaxis; Animals; Disease Models, Animal; Gastric Mucosa; Ovalbumin; Rodentia; Stomach Ulcer

Cells containing immunoglobulin E (IgE) were enumerated and their location in mouse lungs was determined by direct immunofluorescence. Lungs were studied from mice that had been immunized with aerosolized ovalbumin as well as from normal mice and from mice that were exposed to ozone (0.5 or 0.8 ppm) prior to receiving aerosolized antigen. In addition, some mice were immunized intraperitoneally with ovalbumin precipitated in alum. IgE-containing cells were primarily airway-related in normal mice and in mice immunized by the intraperitoneal route. Lungs from aerosol-immunized, and aerosol-immunized ozone-exposed mice showed a more disseminated distribution of IgE-containing cells. Fluorescent cells were counted and numbers were expressed as total cells per square millimeter of lung tissue and as airway-associated cells per millimeter of airway. Total IgE cells increased 9.4-fold in mice that received aerosolized ovalbumin as compared to normal mice. When ozone exposure was added to the effects from aerosolized ovalbumin, the increase of IgE cells over normal was 34.2-fold. IgE cell counts correlated well with anaphylactic sensitivity to intravenous challenge with ovalbumin. The observed enhancement of allergic sensitization by ozone exposure has important implications for human health.

Topics: Administration, Intranasal; Aerosols; Allergens; Anaphylaxis; Animals; Antibodies; Antibody-Producing Cells; Female; Immunoglobulin E; Injections, Intraperitoneal; Lung; Mice; Ovalbumin; Ozone; Passive Cutaneous Anaphylaxis

A model of local ocular anaphylaxis has been developed in the rat. Erythema, oedema, and enhanced retention of radioiodinated rat serum albumin ([125I]-RSA) were noted in ocular adnexal tissues of immunized rats within 5 min of injection of antigen; these changes reached a maximum 15 min after antigen injection. Erythema, oedema, and retention of [125I]-RSA subsided to baseline levels 1--6 hr after challenge. A significant increase in weight of ocular adnexal tissues was seen within 15 min after challenge. The weight increase reached a maximum at 45 min and persisted through 6 hr. Weight approached baseline values by 24 hr. Although antigen was injected into the ocular adnexa and not directly into the globe, the globes of the antigen-injected eyes of immunized rats underwent anaphylaxis, possibly because of absorption of antigen through the sclera. In addition, the adnexa and globes of the contralateral eyes, which did not receive antigen, also underwent anaphylactic changes. These changes were not as marked as those observed in the antigen-injected tissues, but followed the same time-course of development. We conclude that anaphylaxis can be locally induced in ocular tissues, that the onset of anaphylaxis is within minutes, and the effects last for at least 24 hr.

Topics: Anaphylaxis; Animals; Antigens; Disease Models, Animal; Eye Diseases; Ovalbumin; Rats; Rats, Inbred Strains; Serum Albumin, Radio-Iodinated

Topics: Anaphylaxis; Animals; Autacoids; Bronchial Spasm; Drug Interactions; Guinea Pigs; Lipoxygenase Inhibitors; Male; Ovalbumin; Pyrilamine; SRS-A

The influence of Haemophilus influenzae on anaphylactic mediator release from ovalbumin-sensitized isolated guinea pig lungs was investigated. Lungs from H. influenzae-vaccinated animals released prostaglandins and thromboxanes following a smaller dose of ovalbumin than was effective in non-vaccinated animals. Histamine release was significantly increased in 4 day-vaccinated animals but not 1 or 10 days after vaccination, while broncho-constriction was potentiated in 1 and in 4 day-vaccinated animals. This increased histamine release was achieved following 2 micrograms ovalbumin. In contrast, doses of 10 micrograms and 1 mg ovalbumin respectively did not affect and decreased histamine release in the vaccinated group. The inhibition of anaphylactic mediator release by an infusion of 6 x 10(-9) M isoprenaline was significantly attenuated by H. influenzae vaccination. These results indicate an increased sensitivity to antigenic challenge and suggest that the functioning of beta-adrenoceptors was decreased as a result of H. influenzae vaccination.

Topics: Anaphylaxis; Animals; Arachidonic Acids; Asthma; Autacoids; Bradykinin; Bronchial Spasm; Disease Models, Animal; Guinea Pigs; Haemophilus influenzae; Histamine; Histamine Release; In Vitro Techniques; Isoproterenol; Lung; Male; Ovalbumin; Prostaglandins; Rabbits; Rats; Thromboxanes; Vaccination

Anaphylactic shock was induced with ovalbumin in sensitized rats and the relationship between PGE2 and cyclic nucleotides in lung tissue and plasma histamine during anaphylactic shock was studied. PGE2 level and cyclic AMP/cyclic GMP ratio decreased with this ovalbumin-challenge, and the former reached a minimum value 40 sec after the challenge while the latter reached a minimum value 20 sec later. The plasma histamine level was elevated and reached a maximum value concomitant with the minimum value in the cyclic AMP/cyclic GMP ratio. Dibutyryl cyclic AMP elevated the PGE2 level significantly and inhibited the ovalbumin-induced elevation of plasma histamine, however, this effect was abolished by the administration of indomethacin. PGE2 infusion elevated the cyclic AMP level as well as the cyclic AMP/cyclic GMP ratio, in a time-dependent manner, and inhibited the ovalbumin-induced elevation of plasma histamine during 10 min infusion. There was a significant correlation between the cyclic AMP level and the cyclic AMP/cyclic GMP ratio, both elevated by PGE2 infusion. Thus, anaphylactic elevation of the plasma histamine level results from a decrease in the levels of PGE2 in lung tissue rather than a decrease in the cyclic AMP/cyclic GMP ratio, albeit these decreases being coincident during anaphylactic shock.

Topics: Anaphylaxis; Animals; Cyclic AMP; Cyclic GMP; Histamine; Indomethacin; Lung; Male; Ovalbumin; Prostaglandins E; Rats

Haematological and histological studies were made following challenge in 8 monkeys (Macaca irus) sensitized with ovalbumin. Haemagglutinating, but no reaginic antibodies to ovalbumin were demonstrated before challenge. Both platelet and leucocyte counts decreased markedly (-80 and -89%, respectively) within 5 min after challenge. No evidence of haemoconcentration was found. Plasma fibrinogen decreased (-74%), indicating activation of the coagulation system. Histological examination revealed platelets, leucocytes, fibrin and a large number of hyaline globuli ('globular microemboli') in pulmonary capillaries and small arterioles. From their staining properties the globuli were considered to consist mainly of fibrin. Some globuli were also found in the liver and kidneys, but were rarely seen in other organs. It is concluded that the anaphylactic reaction in this experimental model can be classified as aggregate anaphylaxis, and it is suggested that platelet mediators play an important role in the early pulmonary vascular and respiratory response.

Topics: Anaphylaxis; Animals; Antibody Formation; Blood Vessels; Fibrinogen; Haplorhini; Leukocyte Count; Lung; Macaca; Male; Ovalbumin; Platelet Count

1 The inhibitory effects of sodium cromoglycate (SCG) and aminophylline on antigen-induced bronchial anaphylaxis in guinea-pigs, actively sensitized according to different regimens, were examined. 2 SCG (1 mg/kg administered intravenously) reduced the anaphylactic response in animals sensitized with 1 microgram ovalbumin (OA) together with A1(OH)3 100 mg, and challenged at 14 and 40 days after sensitization. If higher doses of antigen (10 micrograms OA together with A1(OH)3 or 5 mg OA on day 0 plus 10 mg OA on day 2) were used for sensitization, the protective effect of SCG was found only in animals tested 14 days after sensitization. 3 A low dose of aminophylline (0.3 mg/kg) that was without a direct bronchodilator effect when tested against a histamine (4 micrograms/kg)-induced bronchospasm, produced an anti-anaphylactic effect. The anti-anaphylactic effect of aminophylline varied slightly with the way the animals were immunized and the time at which they were tested. 4 It is concluded that bronchial anaphylaxis in guinea-pigs sensitized with low doses of ovalbumin is a suitable model for the evaluation of anti-anaphylactic properties of drugs.

Topics: Aminophylline; Anaphylaxis; Animals; Bronchial Spasm; Cromolyn Sodium; Female; Guinea Pigs; Male; Ovalbumin; Respiration; Theophylline; Time Factors

Brown Norway rats have been actively sensitized against hen ovalbumine mixed with anti Bordella pertussis vaccine. After ten to twelve days, IgE are detected in the blood, but no precipitins. Anaphylactic shock induced by i.v. injection of 1 mg.100 g-1 body weight of ovalbumine is caracterized by a vascular collapse, the animal dying in about 15 minutes. This collapse is identical with the same general anaphylactic reaction as observed in the Wistar rats, which have large amounts of precipitins in the blood.

Topics: Anaphylaxis; Animals; Blood Pressure; Diethylcarbamazine; Immunoglobulin E; Indomethacin; Methysergide; Ovalbumin; Promethazine; Rats; Reagins

Guinea pigs sensitized to ovalbumin exhibit signs of respiratory impairment when exposed to an aerosol of the antigen. This response was investigated in anesthetized guinea pigs by determining forced pulmonary mechanics to derive peak expiratory flow rate, forced vital capacity, forced expiratory volume in 0.1 sec, maximal mid-expiratory flow rate and respiratory rate. Measurement of these parameters allows qualitative comparisons to be made with changes that are routinely determined during investigations of human asthma. Exposure of anesthetized guinea pigs to a 3% ovalbumin aerosol for 2 min produced an increase in respiratory rate, a 20% fall in peak expiratory flow rate and maximal mid-expiratory flow rate, a 50% fall in forced vital capacity and a 40% fall in forced expiratory volume in 0.1 sec. This response was reversed by aminophylline. In these respects the response appears to be similar to the acute asthmatic response in humans.

Topics: Aminophylline; Anaphylaxis; Animals; Asthma; Disease Models, Animal; Female; Forced Expiratory Volume; Guinea Pigs; Male; Maximal Midexpiratory Flow Rate; Ovalbumin; Peak Expiratory Flow Rate; Respiration; Respiratory Tract Infections; Vital Capacity

Tracheal smooth muscle (TSM) from an ovalbumin sensitized canine model of allergic asthma showed hypersensitivity and hyper-reactivity to histamine (H) when compared to that from littermate controls in vitro. Mepyramine abolished H responses in TSM of both groups; it also abolished the allergic response to obalbumin of TSM from sensitized dogs. The H2 receptor agonist, 4-methyl histamine (4-MH) caused small dose-related decreases in H contractures but had no effect on carbachol- or K+-induced tension. Metiamide, an H2 antagonist, did not enhance the H contracture, suggesting the 4-MH may not be exerting a relaxant effect since H2 receptors were absent. The maximum H-induced isometric tension was potentiated when the sensitized and control muscle strips were pre-equilibrated with 4-MH. These observations are consistent with the presence in canine TSM of H1 but not relaxant H2 receptors, the release of endogenous H to the tissue during the antigen-antibody reaction, and the competition of H and 4-MH for the H1 receptors. Experiments with specific blockers also indicated that in this model the only transmitter found in the ovalbumin-induced allergic bronchospasm was histamine.

Topics: Airway Resistance; Anaphylaxis; Animals; Asthma; Dogs; Histamine; In Vitro Techniques; Methylhistamines; Metiamide; Muscle Contraction; Muscle, Smooth; Ovalbumin; Pyrilamine; Receptors, Histamine H2; Trachea

This work studies the temporal development of the acute anaphylactic bronchoconstriction in guinea-pigs sensitized to ovalbumin by different regimens, including IgE-antibody promoting ones. The results show that guinea-pigs sensitized with low amounts (1-10 micrograms) of ovalbumin together with alum produce the most pronounced bronchospasm when challenged with an intravenous injection of a low dose of antigen. Examination of the antibody classes by PCA technique shows that guinea-pigs sensitized with small amounts of antigen together with alum produced IgE and IgG1 antibodies. However, in sera from animals immunized with large amounts of antigen, only IgG1 antibodies could be detected.

Topics: Anaphylaxis; Animals; Antigen-Antibody Reactions; Antigens; Bronchi; Bronchial Provocation Tests; Bronchial Spasm; Female; Guinea Pigs; Immunization; Immunoglobulin E; Immunoglobulin G; Injections, Intravenous; Male; Ovalbumin; Passive Cutaneous Anaphylaxis

The effect of intestinal anaphylaxis on goblet cell mucus release was tested in rats immunized with small doses of egg albumin and alum and challenged intraduodenally with antigen. The alteration in vascular and mucosal permeability which accompanies intestinal anaphylaxis was reflected by increased retention of 125I-labelled rat serum albumin in gut wall segments and increased amounts of protein-bound radioactivity in the intestinal secretion from the segments. Intestinal goblet cell mucus was labelled in vivo with 35S. Infusion of antigen, into the duodenum of actively immunized rats led to the appearance of 35S-labelled high molecular weight glycoprotein, presumably of goblet cell origin, in the intestinal secretions. Goblet cell mucus release was dependent on the dose of antigen infused, was antigen-specific and was inhibited by pretreatment of rats with cyproheptidine. Enhanced release of goblet cell mucus was observed in normal rats prepared by intravenous injection of rat antiserum rich in IgE anti-egg albumin antibodies and challenged by intraduodenal infusion of antigen. Prior heating of the antiserum inhibited passive transfer of the reaction; this finding is consistent with the heat lability of IgE antibodies. The latter class of antibodies are presumed to be responsible for intestinal anaphylaxis and its associated mucus release in the model system examined.

Topics: Anaphylaxis; Animals; Antigens; Cell Membrane Permeability; Cyproheptadine; Female; Immunization, Passive; Intestinal Mucosa; Mucus; Ovalbumin; Rats; Secretory Rate

The proposal that some naturally occurring prostaglandins (PGs) or their by-products may be implicated in the pathogenesis of the asthmatic bronchospasm has been suggested. Other PGs may be potentially useful in the treatment of this lung disease. The present investigation compared the bronchodilator effects of PGE1 and PGE2 in pharmacologically constricted experimental animals. In pentobarbital-anesthetized, spontaneously breathing dogs, aerosols of PGE1 and PGE2, 0.0002 to 0.2%, effectively inhibited the increases in pulmonary resistance (RL) and decreases in dynamic lung compliance (CDYN) produced by PGF2 alpha (3.0 micrograms/kg i.v.). PGE2 was found to be more effective than PGE1 in preventing RL responses to PGF2 alpha; however, both bronchodilators were equally effective vs. CDYN changes. These agents inhibited central airway constriction more than peripheral. Transient decreases in systemic arterial pressure and increases in heart rate occurred especially at the higher concentrations. In a group of trained conscious dogs, effective concentrations did not evoke adverse subjective discomfort or irritation. Higher concentrations, i.e., 1.0%, did produce coughing, breathholding, restlessness and altered patterns of breathing. In normal or sensitized guinea pigs, PGE aerosols were effective in reducing the bronchopulmonary provocation produced by histamine or specific antigen. These in vivo results suggest that aerosols of the classical PGEs are effective bronchospasmolytics in laboratory animals and that irritation may be related to concentration.

Topics: Aerosols; Anaphylaxis; Animals; Blood Pressure; Bronchial Spasm; Bronchodilator Agents; Dogs; Dose-Response Relationship, Drug; Female; Guinea Pigs; Heart Rate; Histamine Antagonists; Lung; Male; Ovalbumin; Prostaglandins E; Prostaglandins F

Topics: Anaphylaxis; Animals; Dose-Response Relationship, Immunologic; Immune Tolerance; Immunoglobulin E; Immunosuppression Therapy; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Ovalbumin; Passive Cutaneous Anaphylaxis; Penicillin G; Polyvinyl Alcohol

The percentage of degranulated ocular mast cells in five egg albumin--immunized, systemically challenged rats was compared with that in five egg albumin--immunized, saline-challenged controls. For the lid and orbit, at least 100 mast cells per rat were evaluated. For the conjunctiva, tarsus, limbus, and episclera-sclera, at least 20 were evaluated. For the ciliary body and choroid, all mast cells in 15 sections separated by at least 15 micrometer were examined. The morphology of degranulated and intact mast cells was the same in the experimental and control animals, except for the change in granules. There were significantly more degranulated mast cells in most of the ocular tissues of rats undergoing systemic anaphylaxis than in tissues of controls rats; the increase in degranulated cells was especially striking in the choroid. We concluded that degranulation of mast cells is a measure of anaphylaxis, provided that the number of degranulated mast cells, and not simply the presence of such cells, is considered and compared with appropriate controls.

Topics: Anaphylaxis; Animals; Eye; Male; Mast Cells; Ovalbumin; Rats

Aggregate anaphylaxis was induced by intravenous injection of the specific antigen in eight ovalbumin-sensitized monkeys. Changes in respiratory mechanics, acid-base status and blood gases were studied during the following half hour. Within 1 minute after challenge, a short period of respiratory depression, probably reflex-mediated, was observed. This was followed by hyperventilation, and arterial PCO2 decreased. There was a rapid increase in pulmonary resistance (Rpulm) and a concomitant decrease in pulmonary dynamic compliance (Cdyn), suggesting constriction of smooth muscles in the lung. Rpulm returned to the control value but Cdyn remained depressed, as a result of constriction of small airways and pulmonary congestion. Oxygen saturation in arterial blood decreased slightly due to a marked desaturation of mixed venous blood and increased venous admixture. Progressive metabolic acidosis developed, indicating poor tissue oxygenation and perfusion. The changes observed in this study were not severe enough to cause any major disturbance of the gas exchange in the lungs, despite a severe anaphylactic shock.

Topics: Acid-Base Equilibrium; Anaphylaxis; Animals; Antigens; Carbon Dioxide; Haplorhini; Hydrogen-Ion Concentration; Immunization; Lung Compliance; Macaca; Male; Ovalbumin; Oxygen; Partial Pressure; Respiration; Tidal Volume; Time Factors

One of the organs that can be used to study the Schultz-Dale reaction, is the guinea-pig ileum. The reaction is characterized by a specific pattern: a quick contraction, followed by a quick relaxation and a second, more slow contraction. A description is given of this typical reaction. Selective inhibition of the slow contraction could be obtained using beta-adrenoceptor agonists. Also theophylline inhibited the slow contraction, but this inhibition was only selective within a narrow range of concentration. These findings encourage further investigation about a possible involvement of cyclic nucleotides in the liberation of the mediators involved in the Schultz-Dale reaction of the guinea-pig ileum. Furthermore they provide more information about this preparation which could be used as a screening model for anti-allergic drugs of distinct pharmacological groups.

Topics: Adrenergic beta-Agonists; Albuterol; Anaphylaxis; Animals; Dose-Response Relationship, Drug; Female; Fenoterol; Guinea Pigs; Ileum; Isoproterenol; Male; Ovalbumin; Terbutaline; Theophylline

Complement profiles were established in four groups of Macaca irus monkeys: (I) Aggregate (immune complex) anaphylaxis was induced following immunization, with ovalbumin. Upon challenge, systemic arterial pressure decreased from 115 to 50 mm Hg (mean values) in 10 min. The complement profiles revealed decreases in: C1q to less than 10% of initial value within 5 min; C4 proportional to hypotension; C3 slowly to 60% at 24 h; C5, C6, C7, C8 and factor B to about 80% of initial value in 5--30 min. Conversion products of C3 and factor B were detected on the day of anaphylaxis. In conclusion, mainly the classical and to a lesser extent the alternative pathway, were activated. Following injection of (II) native B 512 dextran, (III) biodegradable starch microspheres, and (IV) saline, no significant changes of complement profiles were seen. Conversion products of C3 and factor B were, however, demonstrable in groups II and III without appearance of clinical signs.

Topics: Anaphylaxis; Animals; Antigen-Antibody Complex; Blood Pressure; Complement C1; Complement System Proteins; Epitopes; Female; Haplorhini; Macaca; Male; Microspheres; Ovalbumin; Polysaccharides; Solubility

Topics: Anaphylaxis; Animals; Antigens, Heterophile; Chickens; Guinea Pigs; Histamine; Histamine Release; Male; Mitochondria, Liver; Monoamine Oxidase; Ovalbumin

Orally administered iodoxamide ethyl (U-42,718) inhibited anaphylactic reactions in a dose-related manner in the following test animals: (1) in the rat PCA reaction, excellent activity (75% inhibition at 0.1 mg/kg) was seen with a duration of activity of 30 min, (2) In the ascaris-sensitive primate (45% inhibition at 1.0 mg/kg) in lung parameters related to increased resistance and decreased compliance which persisted for up to 3 h, and (3) 50 mg/kg protected guinea pigs, sensitized to egg albumin, from lung function changes. Activity in these animal systems indicates that this orally active drug may hold promise in clinical asthma.

Topics: Aerosols; Amino Acids; Anaphylaxis; Animals; Ascaris; Female; Guinea Pigs; Haplorhini; Macaca mulatta; Male; Ovalbumin; Oxamic Acid; Passive Cutaneous Anaphylaxis; Rats; Respiration; Tidal Volume

Aggregate anaphylaxis was induced in eight ovalbumin-sensitized monkeys (Macaca irus). Hemodynamics, blood flow distribution and myocardial performance were studied. Following challenge, severe circulatory shock developed. Systemic arterial and left atrial pressures decreased and pulmonary arterial and right atrial pressures increased. There was a tenfold increase in pulmonary vascular resistance, and cardiac output was markedly reduced (-75%). A redistribution of the blood flow to vital organs (brain, heart and liver) occurred, at the expense of flow to other regions (muscles, kidneys, pancreas and spleen). There was also a redistribution of the blood flow within the myocardium, resulting in an unchanged right ventricular blood flow, despite a decrease in total myocardial blood flow. Right ventricular stroke work was reduced in spite of high filling pressures, whereas the decrease in left ventricular stroke work coincided with low filling pressures. It is concluded that the initial main cause of the low outflow state was an increased resistance in the pulmonary circulation followed by acute right heart failure.

Topics: Anaphylaxis; Animals; Blood Pressure; Cardiac Output; Coronary Circulation; Haplorhini; Heart Rate; Hemodynamics; Immunization; Macaca; Ovalbumin; Pulmonary Circulation; Regional Blood Flow; Stroke Volume; Vascular Resistance

Aggregate anaphylaxis was induced in seven ovalbumin-sensitized monkeys, with high tires of ovalbumin specific haemagglutinating antibodies. After pretreatment with an intravenous (i.v.) injection of 0.25 mg/kg terbutaline (n = 6) or an infusion of isoprenaline (n = 1), anaphylactic shock was induced by i.v. challenge with specific antigen. Haemodynamics, regional blood flows, respiratory mechanics, blood gases and haematological changes were studied during the following 30 min. Severe shock developed following ovalbumin challenge and the cardiac output was reduced by a mean of 74%. Pulmonary vascular resistance increased 11-fold. Pulmonary dynamic compliance decreased, but there was only a minor increase in pulmonary resistance. Hypoxaemia and severe metabolic acidosis developed. Circulating platelets and leucocytes decreased markedly. Three animals died with fulminant pulmonary oedema. In conclusion, the reaction pattern was similar to that found in studies of monkeys that received no prior treatment. However, the occurrence of pulmonary oedema suggests that the effects of large doses of terbutaline on the heart, combined with the high pulmonary vascular resistance, resulted in more severe pulmonary changes than took place in untreated animals.

Topics: Acid-Base Equilibrium; Anaphylaxis; Animals; Antibodies; Haplorhini; Hemodynamics; Immunization; Isoproterenol; Macaca; Ovalbumin; Partial Pressure; Pulmonary Edema; Regional Blood Flow; Respiration; Terbutaline; Vascular Resistance

The authors describe the inhibiting action of mannitol after repeated administration of low subcutaneous doses in a number of experimental immunological models. For example, in the rat it produces a reduction of the secondary arthritis of Freund's adjuvant polyarthritis and also of the pleurisy due to Bordetella pertussis hypersensitivity. In the mouse it reduces the reaction of delayed hypersensitivity to sheep red cells. Its action is also marked against ovalbumin-induced active skin anaphylaxis in the albino guinea-pig and on IgE synthesis in the rat. Moreover, after several injections it produces a reduction of carbon phagocytosis in the mouse. At the doses at which the effect appeared, no action could be found on various models of acute non-immune inflammation, diuresis, blood pressure, hematocrit and protein and plasma sodium levels.

Topics: Acute Disease; Anaphylaxis; Animals; Antibody Formation; Arthritis, Experimental; Blood Pressure; Bordetella pertussis; Freund's Adjuvant; Guinea Pigs; Hypersensitivity, Delayed; Inflammation; Mannitol; Mice; Ovalbumin; Passive Cutaneous Anaphylaxis; Phagocytosis; Pleurisy; Rats

The antagonism by prostacyclin (PG12) and prostaglandin E1 (PGE1) of bronchoconstriction induced by serotonin (5HT), collagen, arachidonic acid (AA) and anaphylaxis, as well as of thrombocytopenia was studied in the guinea-pig. Under conditions where PGE1 prevented bronchoconstriction by 5HT, by collagen or by AA better than the accompanying thrombocytopenia, PG12 was a selective antagonist of bronchoconstriction due to collagen, but failed to interfere with that due to 5HT or to AA. Collagen-induced bronchoconstriction in the guinea-pig is platelet-dependent. PG12 blocks bronchoconstriction by collagen, because it prevents the platelet activation, and fails to interfere with bronchoconstriction by AA, even though it reduces the accompanying thrombocytopenia, because the role of platelets is negligible. PGE1 and PG12 failed to interfere with thrombocytopenia or with bronchoconstriction of anaphylactic shock, and were inactive even when the acute bronchial effect was suppressed by anti-histamine treatment. Anaphylactic thrombocytopenia is beyond the control of agents which stimulate the cyclic AMP system, and involves specific mechanism which are not stimulated in platelet-rich plasma.

Topics: Anaphylaxis; Animals; Arachidonic Acids; Blood Platelets; Bronchi; Collagen; Epoprostenol; Guinea Pigs; Muscle Contraction; Muscle, Smooth; Ovalbumin; Platelet Aggregation; Prostaglandins; Prostaglandins E; Serotonin Antagonists; Thrombocytopenia

Topics: Anaphylaxis; Animals; Aorta; Biological Assay; Bradykinin; Lung; Muscle, Smooth; Ovalbumin; Rabbits; Rats; Species Specificity; Thromboxane A2; Thromboxanes; Vasoconstriction

Homologous guinea pig skin-sensitizing antibodies of the IgG1 class (as characterized by heat stability and persistence in skin for 7 days) were shown to persist systemically for 28-35 days. Persistence was shown by the anaphylaxis induced in guinea pigs following the intracardiac administration of the antiboy and subsequent antigenic challeng by aerosol. Skin-sensitizing antibody of the IgE class, characterized by heat lability and persistence in skin for 14 days, still caused systemic anaphylaxis for 42 days after the intracardiac administration of antibody. The IgG serum fraction from nonimmunized rabbits blocked systemic anaphylaxis in the guniea pig induced by aerosol following the passive transfer of heterologous (rabbit) and homologous IgG antibodies to ovalbumin, but not following the passive transfer of homologous IgE antibodies to ovalbumin.

Topics: Anaphylaxis; Animals; Female; Guinea Pigs; Immunization, Passive; Immunoglobulin E; Immunoglobulin G; Male; Ovalbumin; Skin; Time Factors

In previous studies with isolated perfused rabbit lungs, we observed that human serum albumin (HSA) and ovalbumin, introduced into the isolated lungs as an aerosol, entered the pulmonary circulation antigenically intact. The "inhaled" proteins were also broken down in the lung. When lungs from animals immunized with one protein inhaled the two proteins simultaneously, absorption of intact antigen was specifically reduced, and there was a nonspecific increase in the appearance of metabolites of both proteins in the blood. In the present study, we investigated the antigen-specific and nonspecific effects of two types of hypersensitivity responses on protein absorption across the air-blood barrier of isolated rabbit lungs. In one group of lungs, an acute hypersensitivity response was induced by introducing HSA into the blood perfusing lungs from HSA-immunized rabbits. In another, the rabbits had been previously exposed to chronic HSA aerosol until their lungs exhibited a chronic immunologic inflammatory response. Lungs from both groups were insufflated simultaneously with HSA, and a nonspecific protein, ovalbumin. Lungs in which the acute anaphylactic response was induced showed no alteration in the absorption of either intact protein compared with HSA-immunized controls, but absorbed a somewhat larger quantity of breakdown products of the specific antigen. Lungs undergoing the chronic alveolar inflammation were more permeable to nonspecific protein than were noninflamed lungs. Despite the increased permeability to nonspecific protein, the absorption of antigen was blocked as effectively as in immune but noninflamed controls. In these chronically inflamed lungs, the absorption of antigen breakdown products was enhanced. The results indicate that both immunologic and inflammatory mechanisms may control the amounts of inhaled soluble proteins that reach the blood via the alveolocapillary barrier. Alterations in the absorption of inhaled proteins and their metabolites across the air-blood barrier during certain types of hypersensitivity responses may be of immunologic and pathologic significance.

Topics: Absorption; Alveolitis, Extrinsic Allergic; Anaphylaxis; Animals; Antigens; Capillaries; Female; Male; Ovalbumin; Pulmonary Alveoli; Rabbits; Serum Albumin

Topics: Anaphylaxis; Animals; Female; In Vitro Techniques; Lung; Male; Metiamide; Mice; Ovalbumin; Pyrilamine; Receptors, Histamine; Receptors, Histamine H2

In an attempt to evaluate the role of gastric mucosal defense factors in ulcerogenesis, we measured the levels of glycoproteins in the mucosa as well as mucosal cell turnover in the preulcerous phase and compared these parameters to the normal mucosa in the same animal. Ovalbumin-presensitized Praomys (Mastomys) natalensis were challenged in the gastric wall with ovalbumin and a gastric ulcer developed at the challenge site 3 days later as a result of a mucosal anaphylactic reaction. This model enabled us to study the events occurring at the site of a future ulceration. Gas-liquid chromatographic determination of mucosal glycoproteins showed that the normal and preulcerous mucosae had similar levels. Cell turnover, determined by [3H]thymidine incorporation, was stimulated as a result of the preulcerous anaphylactic reaction at 24 hours postchallenge whereas at 48 hours the values were not different from those obtained in controls. These results suggest that the pathogenesis of anaphylactic gastric ulcer involves a change in cell turnover but no changes in the production of gastric mucus.

Topics: Anaphylaxis; Animals; Disease Models, Animal; Female; Gastric Mucosa; Glycoproteins; Kinetics; Male; Monosaccharides; Ovalbumin; Rodentia; Stomach Ulcer; Thymidine; Time Factors

Topics: Anaphylaxis; Animals; Brompheniramine; Chromones; Dose-Response Relationship, Drug; Ethers; Female; Guinea Pigs; Histamine; Indomethacin; Lung; Male; Metiamide; Ovalbumin; Receptors, Histamine H1

1 The anaphylactic reaction of the guinea-pig ileum, the so called Schultz-Dale reaction, shows a biphasic response: a short rapid contraction followed by a partial relaxation and a slow contractile response. 2 Dose-response curves with ovalbumin as an antigen were obtained for the quick and slow contraction of this anaphylactic reaction. 3 Mepyramine (1 microgram/ml) blocked the rapid first contraction, but failed to abolish the slow one in about 50% of the animals studied. 4 The SRS-A antagonist, FPL 55712, significantly depressed the slow sustained contraction during the Schultz-Dale reaction. Disodiumcromoglycate was without effect on both phases when it was added 5 min before addition of the antigen. However, when added simultaneously with the antigen it produced a 30% suppression of the slow phase in the highest concentration used.

Topics: Anaphylaxis; Animals; Female; Guinea Pigs; Histamine; Ileum; In Vitro Techniques; Male; Ovalbumin; SRS-A

A selective inbreeding of approximately 24 generations of albino guinea pigs by brother x sister mating has resulted in two strains, registered IMM/S and IMM/R, with high and low responsiveness, respectively, to ovalbumin-induced respiratory anaphylaxis. The two guinea pig strains differed in their ability to be immunized by the inhalation of antigen and produce antibodies, as well as to develop respiratory anaphylaxis. A correlation between the strength of the anaphylactic reactions and the amount of hemagglutinating antibodies produced was observed. When immunization was carried out by an intradermal injection of ovalbumin (OA), even in small doses incorporated in FCA, guinea pigs from both strains produced hemagglutinating antibodies in nearly the same amount. These antibodies do not influence the ability of the animals to react with a high respectively low anaphylactic response on subsequent challenge by inhalation of OA, neither in the actively sensitized animals nor in passively sensitized animals. However, with repeated inhalations of OA, desensitization occurred in the intradermally immunized high-responders, while the passively immunized high-responders could be provoked several times without any signs of desensitization. No systematical differences between the two strains with regard to sensitivity to inhalations of histamine were demonstrated. The low responders were found to be less resistant to infections than high-responders.

Topics: Aerosols; Anaphylaxis; Animals; Antibodies; Antibody Formation; Female; Fetal Death; Guinea Pigs; Hemagglutination; Immunity, Maternally-Acquired; Immunization; Inbreeding; Litter Size; Ovalbumin; Pregnancy; Respiratory Hypersensitivity

Topics: Anaphylaxis; Animals; Drug Evaluation; Guinea Pigs; Histamine H1 Antagonists; Hypersensitivity; Male; Mast Cells; Ovalbumin; Piperazines

Lungs from rabbits sensitized to ovalbumin or bovine gamma-globulin were isolated and perfused with autologous blood. The response to antigen challenge via the perfusate was immunologically specific and characterized by a marked increase in perfusion resistance, a moderate increase in airway resistance and a small decrease in lung compliance. The response could also be elicited by specific antigen challenge in lungs from sensitized rabbits perfused with blood from normal rabbits and in lungs from normal rabbits perfused with blood or plasma from sensitized rabbits. The magnitude of the response was greater when blood or plasma from sensitized animals was used as the perfusate. Therefore, blood and/or plasma factors appear to be the major contributors to the response.

Topics: Airway Resistance; Anaphylaxis; Animals; Antigens; gamma-Globulins; In Vitro Techniques; Lung; Lung Compliance; Ovalbumin; Perfusion; Pulmonary Circulation; Rabbits; Vascular Resistance

Topics: Anaphylaxis; Animals; Catechol O-Methyltransferase; Epinephrine; Guinea Pigs; In Vitro Techniques; Lung; Male; Monoamine Oxidase; Ovalbumin

Antigen challenge of rats, sensitized by intraperitoneal injection with rat anti-serum, did not result in a detectable increase in the 5-hydroxytryptamine (5-HT) levels in their peritoneal fluids over the background level induced by sensitisation alone. The maximum amount of extravasation produced by intraperitoneal injection of 5-HT into passively sensitised rats was less than that produced by antigen or histamine, and the doses of 5-HT producing these levels of extravasation produced an produced an increase of 5-HT concentrations in the peritoneal fluids. Therefore, 5-HT is unlikely to make much direct contribution to the extravasation produced during rat passive peritoneal anaphylaxis. However, when given intraperitoneally to rats, 5-HT potentiates the extravasation produced by histamine.

Topics: Anaphylaxis; Animals; Ascitic Fluid; Coloring Agents; Dose-Response Relationship, Immunologic; Histamine; Male; Methysergide; Ovalbumin; Rats; Serotonin; SRS-A

Topics: Anaphylaxis; Animals; Female; Freund's Adjuvant; Guinea Pigs; Haptens; Histamine; Hypersensitivity, Immediate; Male; Neuraminic Acids; Ovalbumin; Platinum; Serotonin

Studies were performed in animals to establish whether antigen prefeeding could present homocytotropic antibody synthesis and the induction of gastric ulcer resulting from mucosal anaphylaxis. A single digestive exposure to 1 or 10 mg ovalbumin induced a state of specific immunologic tolerance. Inhibition of the formation of specific reagins was shown by the study of mast cell degranulation. Tolerant animals presented a reduced incidence of gastric ulcer after subsequent mucosal challenge. These results are important for the development of methods of prevention and treatment of allergic diseases.

Topics: Anaphylaxis; Animals; Antigens; Female; Gastric Mucosa; Immune Tolerance; Male; Mast Cells; Ovalbumin; Reagins; Rodentia; Stomach Ulcer

Topics: Amine Oxidase (Copper-Containing); Anaphylaxis; Animals; Cyclic AMP; Guanidines; Guinea Pigs; Heparin; Histamine; Histamine Release; Lung; Ovalbumin; Prostaglandins E; Prostaglandins F

Topics: Anaphylaxis; Animals; Clemastine; Cromolyn Sodium; Dose-Response Relationship, Drug; Histamine H1 Antagonists; Histamine Release; Ovalbumin; p-Methoxy-N-methylphenethylamine; Passive Cutaneous Anaphylaxis; Piperidines; Rats; Thiophenes

Topics: Anaphylaxis; Animals; Blood Pressure; Cardiac Output; Female; Haplorhini; Heart Rate; Hemodynamics; Histamine; Indomethacin; Macaca mulatta; Male; Ovalbumin; p-Methoxy-N-methylphenethylamine; Prostaglandins E; Prostaglandins F; Time Factors

Topics: Anaphylaxis; Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Edema; Edema Disease of Swine; Gallbladder; Gastric Mucosa; Immunization; Injections, Intravenous; Larynx; Ovalbumin; Swine; Swine Diseases; Vitamin E Deficiency

50 guinea pigs were allergized three times in 3 days intervals by subcutaneous injection of 25% solution of egg-white in physiological saline in a dose of 0-1 ml/100 g of body weight. On the 21 day after the last injection the animals were exposed to aerosol of antigen of egg-white. 11 animals died in acute anaphylactic shock. The control group consisted of 12 guinea pigs which received subcutaneously a solution of physiological sodium chloride of the same dosis--0-1 ml/100 g of body weight and were also exposed to the allergen, together with the experimental group. The removed parathyroids together with the thyroid gland were studied with histologic and cytoenzymatic methods. The activity of alkaline and acid phosphomonoesterase, nonspecific AS-naphtol acetate esterase, succinic (SDH), lactic (LDH) and D-L-alfaglicerophosphate dehydrogenase (alpha-GPD) were tested. No morphological changes in the parathyroids of guinea pigs in anaphylactic shock were found. Instead a decrease of the enzymatic activity of dehydrogenases was found, what might be connected with the decrease of metabolic activity of the cells. The decrease of alkaline phosphatase activity in the endothelial cells of the capillaries was another finding. It is likely that in an acute anaphylactic shock in guinea pigs only functional changes develop which have not counterparts in histology visible under the light microscope.

Topics: Acid Phosphatase; Acute Disease; Alkaline Phosphatase; Anaphylaxis; Animals; Glycerolphosphate Dehydrogenase; Guinea Pigs; Histocytochemistry; L-Lactate Dehydrogenase; Naphthol AS D Esterase; Ovalbumin; Parathyroid Glands; Succinate Dehydrogenase

Lungs from control and sensitized guinea pigs were perfused via the pulmonary artery with Tyrode's solution. Infusion of equimolar concentrations (3x10(-9) to 3x10(-6 M) of 3H-1-norepinephrine (NE) and 14C-urea was started 1 min after injection of 1 ml 0.9% NaCl or 50 mg ovalbumin in 1 ml 0.9% NaCl and continued for 15 min. Anaphylactic lungs retained more urea, NE, and NE metabolites than control lungs at all NE concentrations and the proportion of unchanged NE was higher. Phenoxybenzamine decreased the 3H/14C ratio due to decreased 3H accumulation. Cocaine affected predominantly the control lungs. The results indicate that anaphylaxis increased the net uptake of NE in the lung and decreased the metabolism of retained NE.

Topics: Anaphylaxis; Animals; Antigens; Cell Membrane Permeability; Cocaine; Guinea Pigs; Immunization; Lung; Norepinephrine; Ovalbumin; Phenoxybenzamine; Urea

The protective effects of pretreatment with zinc sulphate aerosols against bronchoconstriction induced by egg albumen or histamine aerosols were assessed in sensitized or non-sensitized guinea-pigs respectively. Pretreatment with an adequate concentration of zinc sulphate aerosol significantly prolonged the time of onset of bronchoconstriction in sensitized guinea-pigs challenged with egg albumen, but did not appreciably alter the onset time of histamine-induced bronchoconstriction in non-sensitized animals. These findings suggest that zinc aerosols may be of prophylactic value against bronchoconstriction of allergic origin.

Topics: Aerosols; Anaphylaxis; Animals; Bronchial Spasm; Female; Guinea Pigs; Histamine; Male; Ovalbumin; Zinc

Antibodies (ABS) against hydroxyethylstarch (HES) were raised in rabbits by immunization with HES-bovine serum albumin conjugate. ABS against HES were demonstrable by gel diffusion, passive hemagglutination (PH) and passive cutaneous anaphylaxis (PCA); specificity was confirmed by inhibition of PH and neutralization of PCA. No ABS against starch could be induced in comparative experiments. Non-immunogenicity of starch was attributed to its structural similarity with glycogen, widely distributed in animal species. Absence of cross-reactivity of anti-HES ABS with starch, amylopectin and glycogen and strong reactivity with 2-hydroxypropylstarch (DS = 0.65) and HES (DS = 0.7-1.2) indicate that hydroxyethyl substitution created antigenic determinants and conferred new immunochemical identity on the modified starch molecule. Anti-HES ABS represent specific analytical tools for the identification and quantitation of HES in biological material.

Topics: Anaphylaxis; Animals; Antibody Formation; Cross Reactions; Hemagglutination Tests; Hydroxyethyl Starch Derivatives; Immunodiffusion; Ovalbumin; Rabbits; Serum Albumin; Starch

The present paper describes an ultrastructural study of two different kinds of behavior of mouse mast cells during two immunological reactions induced by transplantation antibodies: the direct allogeneic anaphylactic degranulation and the serocytotoxicity. In both situations, the same alloantigens, born by the mast cells themselves, are the targets of the reaction, but the first one is mediated by anaphylactic alloantibodies whereas the second one is mediated by cytotoxic alloantibodies in the presence of complement. The comparison of the ultrastructural aspects of the cells in these two systems demonstrated that mast cells can behave in two different ways depending on the nature of the immunological agents utilized. First, a physiological degranulation process with active granule expulsion was observed. This process was shown to be identical to the one induced in classical in vitro anaphylaxis or by histamine releasers such as compound 48/80. A second type of behavior was a lethal, complement-dependent, cell lysis without active granule expulsion.

Topics: Anaphylaxis; Animals; Antigen-Antibody Reactions; Complement System Proteins; Cytotoxicity Tests, Immunologic; Histocompatibility Antigens; Inclusion Bodies; Isoantibodies; Mast Cells; Mice; Ovalbumin; p-Methoxy-N-methylphenethylamine

An animal model of food allergy has been developed in which some aspects of the allergic response could be quantified and the effects of various drugs evaluated. The change in permeability of the intestinal tract of actively sensitized rats, after oral challenge with the sensitizing antigen, was the parameter measured. Rats were sensitized by injection of egg albumin and B. pertussis vaccine to induce reaginic antibody to egg albumin. Two weeks after sensitization, 125I-labelled bovine serum albumin (125I-labelled BSA) was injected intravenously, followed by oral challenge with egg albumin. Pieces of intestinal tissue were obtained and the amount of 125I-labelled BSA determined in a gamma counter. The amount of 125I-labelled BSA in the intestinal tissue of sensitized and challenged rats regularly showed an increase of greater than 100% above values for control rats.

Topics: Anaphylaxis; Animals; Antigens; Capillary Permeability; Cromolyn Sodium; Cyproheptadine; Disease Models, Animal; Female; Food Hypersensitivity; Hemocyanins; Immunoglobulin E; Intestines; Mast Cells; Ovalbumin; Pertussis Vaccine; Rats

In mepyramine treated, ovalbumin sensitized anaesthetized guinea pigs protracted anaphylactic shock was produced by i.p. injection of antigen, and serum creatine kinase (CK) activities were determined 4, 6, or 17 hrs thereafter. Significant increases above nonsensitized controls were obtained. In nonanaesthetized guinea pigs shock course and serum CK increase were considerably accelerated. Histamine increased the serum CK only when given in high amounts (10 mg/kg) s.c., in the presence or absence of mepyramine. I.p. injection of histamine in mepyramine treated animals had no effect. Adrenaline (1 or 10 mg/kg) given as a s.c. depot in oil produced a significant increase of serum CK, as well as noradrenaline (0.1, 1, or 10 mg/kg). Dibenamine reduced the effect of adrenaline. In isolated perfused guinea pig hearts a significant CK liberation occurred already within the first hour after eliciting anaphylaxis. Nonanaphylactic hearts released CK too, but significant amounts were obtained only in the total 4 hrs after ovalbumin administration. Isolated anaphylactic hearts incubated in Tyrode solution liberated significantly more CK than did nonsensitized control hearts. The findings are discussed in view of a possible myocardial damage in anaphylaxis.

Topics: Anaphylaxis; Animals; Antigens; Catecholamines; Creatine Kinase; Dibenzylchlorethamine; Epinephrine; Female; Guinea Pigs; Histamine; Male; Myocardium; Norepinephrine; Ovalbumin; Pyrilamine

Topics: Anaphylaxis; Animals; Guinea Pigs; Isoproterenol; Male; Ovalbumin; Seizures

We were unable, passively, to transfer reactivity against dextran to the skin or peritoneal mast cells of non-dextran-reactive rats, by using serum or material eluted at pH 3 from mast cells of spontaneously dextran-reactive rats. When the dextran-reactive donor rats had also been immunized against egg albumin (EA) with pertussis vaccine (inducing IgE anti-EA antibody), passive sensitivity against EA (but not against dextran) could easily be transferred. The results indicated that the anti-dextran reactivity is not due to IgE antibody. Systemic reactions against dextran and EA differed in pattern, supporting the concept that the two substances acted through different mechanisms.

Topics: Anaphylaxis; Animals; Antibodies; Dextrans; Immunization, Passive; Immunoglobulin E; Male; Mast Cells; Ovalbumin; Rats; Skin Tests

Anaphylactic shock induced in rabbits by the preliminary injury of various areas of the medial hypothalamus coursed more severly than in control. Irrespective of the localization of the foci of injury a more pronounced hypotensive reaction and a slower compensatory elevation of the blood pressure occurred in response to the administration of the reactive dose of the antigen. The severity of anaphylactic shock depended on the time lapse from the moment of hypothalamic injury to the moment of administration of the reactive dose of the antigen.

Topics: Anaphylaxis; Animals; Antibodies; Dose-Response Relationship, Immunologic; Hypothalamus; Hypothalamus, Middle; Immunization; Ovalbumin; Rabbits; Time Factors

Topics: Anaphylaxis; Animals; Dose-Response Relationship, Drug; Guinea Pigs; Histamine H1 Antagonists; Histamine Release; In Vitro Techniques; Male; Muscle Contraction; Ovalbumin; Phenylpropionates; SRS-A; Trachea

Topics: Adrenergic beta-Agonists; Adrenergic beta-Antagonists; Anaphylaxis; Animals; Freund's Adjuvant; Guinea Pigs; Heart Atria; Histamine Release; In Vitro Techniques; Lung; Ovalbumin; Receptors, Adrenergic; Stimulation, Chemical; Trachea

Topics: Anaphylaxis; Animals; Antibodies; Antibody Formation; Dextrans; Histamine Release; Horses; Immunization Schedule; Immunoglobulin E; Ovalbumin; Passive Cutaneous Anaphylaxis; Rats; Reagins; Serotonin; Vaccines

Topics: Anaphylaxis; Animals; Antigens; Cattle; Cattle Diseases; Freund's Adjuvant; Histamine; Histamine Release; Horses; Hypertension, Pulmonary; Immune Sera; Immunization; In Vitro Techniques; Injections, Intravenous; Injections, Subcutaneous; Kinins; Lung; Muscle Contraction; Ovalbumin; Serotonin; Skin Tests

Cattle were more readily sensitised than guinea pigs to carboxymethylcellulose. Freund's complete adjuvant enhanced, but was not essential for, sensitisation. Schultz-Dale responses were obtained from pulmonary tissues of sensitised cattle but their sera failed to induce passive cutaneous anaphylaxis. Cattle could possibly be sensitised by carboxymethylcellulose contained in drug formulations.

Topics: Anaphylaxis; Animals; Antigens; Bordetella pertussis; Carboxymethylcellulose Sodium; Cattle; Cattle Diseases; Drug Hypersensitivity; Freund's Adjuvant; Guinea Pigs; Histamine Release; Injections, Intradermal; Injections, Intramuscular; Injections, Intraperitoneal; Injections, Intravenous; Methylcellulose; Muscle Contraction; Ovalbumin; Passive Cutaneous Anaphylaxis

The relationship of glycogen and glucose to anaphylactic histamine release from chopped sensitized guinea pig lung in vitro was studied. A parallelism was observed between the total amount of glycogen in the sensitized lung and the total amount of histamine released from the lung by antigen-antibody reactions. Removal of glucose from the medium for tissue suspension resulted in reduction in histamine release. Depletion of glycogen and/or glucose from the system was associated with (1) abolition of the inhibition of histamine release by isoproterenol and high concentrations of dibutyryl cyclic adenosine monophosphate (AMP) and (2) increase in the rate of enhancement of histamine release by lower concentrations of dibutyryl cyclic AMP. The results indicate that (1) glycogen may be one of the ultimate energy sources for anaphylactic histamine release, and (2) the presence of adequate amounts of glycogen and/or glucose in the sensitized tissue is necessary for the normal beta adrenergic effects on the histamine release in vitro from sensitized lung fragments.

Topics: Anaphylaxis; Animals; Antigen-Antibody Reactions; Cyclic AMP; Glucose; Glycogen; Guinea Pigs; Histamine; Histamine Release; Hypoxia; Immune Sera; In Vitro Techniques; Injections, Intradermal; Isoproterenol; Lung; Male; Ovalbumin; Serum Albumin, Bovine

A four-fold transient rise in c-AMP levels was seen when sensitized guinea-pig lungs were challenged with antigen in vitro. This rise in c-AMP also occurred in vivo and was shown to be due to release of Prostaglandin E2. This conclusion is supported by the finding that inhibitors of prostaglandin synthesis (Indomethacin and Poly phloretin phosphate) prevent the rise in c-AMP while neither ICI 74, 917, an inhibitor of histamine release, nor antihistamines had any effect on the c-AMP levels.

Topics: Anaphylaxis; Animals; Burimamide; Cyclic AMP; Guinea Pigs; Histamine; Immunization; Indomethacin; Isoproterenol; Lung; Ovalbumin; Polyphloretin Phosphate; Propranolol; Prostaglandins E; Prostaglandins F; Pyrilamine; Serotonin

A detailed analysis of the lipid content of guinea-pig lung following anaphylaxis in vivo induced by aerosolized antigen showed a significant reduction in all fractions. Anoxia induced by nitrogen produced reductions in the partial glycerides and ethanolamine phospholipid. Exposure to an aerosol of histamine caused a reduction in all but the choline phospholipid and sphingolipid fractions. It was concluded that the losses of choline phospholipid and sphingolipid result from the anaphylactic reaction and not from subsequent changes.

Topics: Aerosols; Anaphylaxis; Histamine; Hypoxia; Lipids; Lung; Ovalbumin; Phospholipids; Time Factors

The study was undertaken to discover whether the catecholamines released as a result of the stress and hypoxia of anaphylaxis were responsible for the concomitant loss of lipid from the lung. A method is described whereby the respiratory rate and volume and heart-rate of conscious sensitized guinea-pig were measured and the electrocardiogram recorded during anaphylaxis induced by aerosolized antigen. After 7 days or more, some animals were anaesthetized with pentobarbitone and respiration was artificially maintained at the level recorded in the conscious state, whilst the quantity of catecholamines liberated during anaphylaxis was assayed using an extra-corporeal blood circulation to superfuse smooth muscle preparations. In other animals of the same group, it was shown that intravenous infusion of adrenaline in a similar quantity to that detected in the circulation following anaphylaxis (0.3 mug min-(-1) for 40 min) caused losses of triglyceride and partial glycerides from the lungs. Thus, the loss of choline-containing phospholipid was attributed to the direct effects of the anaphylactic reaction on the lung tissue.

Topics: Anaphylaxis; Animals; Catecholamines; Chick Embryo; Electrocardiography; Epinephrine; Guinea Pigs; Heart Rate; In Vitro Techniques; Lipids; Lung; Male; Muscle Tonus; Muscle, Smooth; Ovalbumin; Oxygen Consumption; Rats; Rectum; Respiration; Stomach

Histamine-induced paw oedema and anaphylactic shock were studied simultaneously in ovalbumin-sensitized guinea-pigs and cinnarizine and flunarizine were evaluated quantitatively with regard to protection from the two types of challenge. Both compounds were markedly more active in preventing lethal anaphylaxis (ED50's of 0.67 and 0.53 mg/kg OR) than in reducing histamine oedema (ED50's of 2.77 and 1.54 mg/kg OR). The high anti-anaphylactic potency after oral administration may be an important finding in view of the therapeutic applications of cinnarizine and flunarizine.

Topics: Anaphylaxis; Animals; Cinnarizine; Female; Guinea Pigs; Histamine; Histamine H1 Antagonists; Immune Sera; Male; Ovalbumin; Piperazines

The syntheses of trans-3-(4-oxo-4H-1-benzypyran-3)acrylic acid and a number of analogs shown to be highly active in antiallergic bioassays are described. These compounds are of possible value in the treatment of asthma. The structural requirements for biological activity are discussed with reference to the type of the substituents on the chromone ring or positions of linkage of the acrylic acid on the pyrone ring.

Topics: Acrylates; Anaphylaxis; Animals; Bacillus; Benzopyrans; Dose-Response Relationship, Drug; Hypersensitivity; Immune Sera; Male; Ovalbumin; Passive Cutaneous Anaphylaxis; Rats; Stereoisomerism; Structure-Activity Relationship

Effects of cortisol and anaphylaxis on the uptake of catecholamines (CA) in the guinea pig lung have not been investigated previously. Sensitized and healthy animals were randomly killed, catheters were inserted into the pulmonary artery and vein, and the preparation was perfused with Tyrode. Half of the animals received 50 mg. of cortisol 2 hours before the procedure. H3-epinephrine (E) or norepinephrine (NE), 10 ng. per milliliter, was infused for 6 minutes. Infusion was started 15 seconds prior to challenge with ovalbumin or NaCl. Total -H3 and NE(E)-H3 were determined in the lung homogenates. Results showed (1) 6 to 14 per cent of circulating CA were retained by the lung. (2) In healthy animals cortisol inhibited NE uptake by 35 per cent and E uptake by 15 per cent. (3) Anaphylaxis increased NE and E accumulation by 10 and 19 per cent, respectively. (4) Regardless of experimental conditions approximately 40 per cent of NE and 30 per cent of E taken up were recovered unchanged.. (1) There is significant uptake of CA in the lung. (2) One of the mechanisms of therapeutic effect of cortisol in asthma might be its inhibitory effect on CA uptake. (3) Increased CA accumulation during anaphylaxis could be beneficial by increasing the local concentration of amines, or detrimental by decreasing availability of CA, depending on the uptake site and cell type and degree of subsequent metabolism. (4) Cortisol and anaphylaxis per se appear not to change degradation of CA.

Topics: Anaphylaxis; Animals; Epinephrine; Guinea Pigs; Hydrocortisone; Lung; Norepinephrine; Ovalbumin; Perfusion; Placebos

The local anaphylactic reaction and the effects of histamine during blocking of the slow sodium-calcium channels by isoptine were investigated in the spontaneously contracting oracle of the atrium of a guinea pig previously sensitized to egg albumin. Simultaneously with the intracellular recording of the potentials, isometric contractions of the preparation were recorded by means of a mechanotron. The investigation showed that egg albumin (0.2 mg/ml) and histamine (0.1 mg/ml) are antagonists of isoptine (2-16 mg/liter) as regards its effect on automatic contraction and duration of the action potential. It is postulated that this anaphylatic reaction is based on activation of the slow sodium-calcium channels in the surface membrane of the myocardial fibers.

Topics: Action Potentials; Anaphylaxis; Animals; Calcium; Guinea Pigs; Heart; Histamine; In Vitro Techniques; Myocardium; Ovalbumin; Sodium; Verapamil

Sodium meclofenamate was compared to saline for efficacy in preventing and treating experimentally induced, acute, systemic anaphylaxis in cattle. Respiratroy changes were shown to be reduced to the greatest extent. Lacrimation and collapse were not affected. The timing and routes of administration giving maximum efficacy were those which gave maximum plasma levels of the drug closest to the time of exposure of the animal to the specific antigen.

Topics: Administration, Oral; Anaphylaxis; Animals; Antigens; Cattle; Cattle Diseases; Cough; Injections, Intravenous; ortho-Aminobenzoates; Ovalbumin; Respiratory Insufficiency; Salivation; Toluene

Bilateral electrolytic lesions were placed in the anterior basal hypothalamus of male Hartley-strain guinea pigs. The animals with anterior hypothalamic lesions and a group of sham-operated controls were sensitized 5-10 days postoperatively with ovalbumin in modified Freund's adjuvant. At 18-22 days following sensitization both groups were randomly divided into three subgroups and challenged by intrajugular injections of three different antigen doses. Anaphylactic death and the severity of anaphylaxis in the survivors were recorded. Antibody titers were determined prior to challenge with use of the passive cutaneous anaphylaxis technique. Serial sections of each brain were made for lesion localization. Significant protection against anaphylaxis was found in guina pigs with symmetrical lesions in the anterior hypothalamus. No significant differences in antibody titers were observed between the lesion and sham-operated groups. There were no significant differences in the response of isolated muscle strips from anterior-lesioned and sham-operated guinea pigs to exogenous histamine. Anterior hypothalamic lesions of size and location comparable to those that provided protection against lethal anaphylaxis did not modify the anaphylactic response of isolated ileum from actively sensitized animals or following passive sensitization in vitro.

Topics: Anaphylaxis; Animals; Antibodies; Antigens; Freund's Adjuvant; Guinea Pigs; Histamine; Hypothalamus; Ileum; Immunity, Maternally-Acquired; Immunization; Male; Muscles; Ovalbumin; Passive Cutaneous Anaphylaxis

The administration of egg albumin to rabbits sensitized to this antigen caused marked increases in the arterial concentration of lactate, glucose and glycerol, but no change in the arterial FFA level. Antigen administration had no effect in non-sensitized rabbits. Phentolamine (3 mg/kg) or propranolol (1 mg/kg) did not significantly alter the responses to egg albumin in sensitized rabbits. Noradrenaline or sympathetic nerve stimulation decreased blood flow but caused no significant change in lipolysis in rabbit epigastric adipose tissue in situ. It is therefore questionable if catecholamines are the major cause of the observed metabolic consequences of the anaphylactic reaction in the rabbit. These metabolic events, i.e. increased lactate levels, lipolysis, and reesterification of fatty acids, are similar to those reported during hemorrhagic or endotoxin shock in dogs, in spite of specied-differences and the difference in the genesis of the shock.

Topics: Adipose Tissue; Anaphylaxis; Animals; Blood Glucose; Electric Stimulation; Fatty Acids, Nonesterified; Glycerol; Lactates; Male; Norepinephrine; Ovalbumin; Phentolamine; Propranolol; Rabbits; Stimulation, Chemical

Changes of electrical activity (intracellular records) of guinea pig heart auriculus were studied during experimental cardiac anaphylaxis (ovalbumine being used as an antigen). Fast Na channels of the myocardial fibers having been depressed by long-standing depolarization in K+-rich (20 mM) Tyrode solutions, only the low-amplitude slow responses to brief stimuli were recorded. Addition of ovalbumine (2.10(-4) g/ml), histamine (1.10(-4) g/ml) or adrenaline (5.10(-6) g/ml) to the K-rich solution led to increase of both the amplitude and the duration of the responses. These data supported the hypothesis on the principal role of slow Na--Ca channels in the mechanism of the changes in the electrical activity of the myocardial fibers during cardiac anaphylaxis.

Topics: Anaphylaxis; Animals; Electrophysiology; Epinephrine; Guinea Pigs; Heart; Histamine; Myocardium; Neural Conduction; Ovalbumin; Sodium

Anaphylaxis was induced in the lizard, Calotes versicolor by egg albumen. The symptoms were similar to those found in other species. The maximum mortality occurred 14 days after sensitization and the reaction was specific. Splenectomy before sensitization abrogated the manifestations of anaphylaxis.

Topics: Anaphylaxis; Animals; Female; Lizards; Male; Ovalbumin; Splenectomy

Topics: Anaphylaxis; Animals; Castration; Estradiol; Female; Guinea Pigs; Heart Atria; Histamine; Histamine Release; Immunization; Kinetics; Organ Specificity; Ovalbumin; Ovary; Oviducts; Progesterone; Temperature; Time Factors

Topics: Absorption; Anaphylaxis; Animals; Female; Guanidines; Guinea Pigs; Histamine; Histamine Release; Injections, Intravenous; Jugular Veins; Liver; Male; Ovalbumin; Zinc

Topics: Anaphylaxis; Animals; Antigens; Autacoids; Bronchi; Epinephrine; Guinea Pigs; Histamine; Histamine H1 Antagonists; Histamine Release; In Vitro Techniques; Indomethacin; Isoproterenol; Lung; Ovalbumin; Perfusion; Propranolol; Prostaglandins; Radioimmunoassay; Sympathomimetics; Time Factors; Vasoconstrictor Agents

Topics: Aerobiosis; Anaerobiosis; Anaphylaxis; Animals; Carbon Dioxide; Carbon Radioisotopes; Dextrans; Glucose; Helium; Histamine Release; Lactates; Mast Cells; Nitrogen; Oligomycins; Ovalbumin; Oxidation-Reduction; Oxygen Consumption; p-Methoxy-N-methylphenethylamine; Phosphatidylserines; Rats

Topics: Aerosols; Anaphylaxis; Animals; Antigens; Asthma; Eosinophilia; Guinea Pigs; Histamine Release; Mast Cells; NAD; Niacinamide; Ovalbumin; p-Methoxy-N-methylphenethylamine

Topics: Anaphylaxis; Animals; Bronchial Spasm; Constriction; Epinephrine; Female; Guinea Pigs; Histamine Release; Indomethacin; Injections, Intraperitoneal; Isoproterenol; Lung; Male; Ovalbumin; Perfusion; Propranolol; Prostaglandin Antagonists; Prostaglandins; Pulmonary Alveoli; SRS-A; Tritium

Topics: Anaphylaxis; Animals; Bucladesine; Cyclic AMP; Cyclic GMP; Depression, Chemical; Dose-Response Relationship, Drug; Female; Fluorometry; Histamine Release; Mast Cells; Ovalbumin; Rats

Topics: Anaphylaxis; Animals; Antibodies; Antigens; Biological Assay; Chemotaxis; Chromatography, Gel; Eosinophils; Female; Guinea Pigs; Histamine; Histamine Release; Ileum; Immunization, Passive; Immunoglobulin G; In Vitro Techniques; Male; Molecular Weight; Ovalbumin; Pronase; Skin; SRS-A; Temperature; Time Factors

Topics: Aerosols; Anaphylaxis; Animals; Bile; Bronchial Spasm; Guinea Pigs; Histamine; Histamine H1 Antagonists; Methods; Ovalbumin; Time Factors

Topics: Acetylcholine; Alkaloids; Amines; Anaphylaxis; Animals; Antigens; Atropine; Benzyl Compounds; Dimethylamines; Dose-Response Relationship, Drug; Guinea Pigs; Histamine; Histamine H1 Antagonists; Ileum; Indoles; Male; Methysergide; Muscle Contraction; Muscle, Smooth; Ovalbumin; p-Methoxy-N-methylphenethylamine; Serotonin; Trachea

Topics: Aerosols; Anaphylaxis; Animals; Antigens; Blood Pressure; Bronchi; Bronchodilator Agents; Carbachol; Cyclopentanes; Dose-Response Relationship, Drug; Fatty Acids; Guinea Pigs; Histamine; Histamine H1 Antagonists; In Vitro Techniques; Injections, Intravenous; Isoproterenol; Muscle, Smooth; Ovalbumin; Propranolol; Prostaglandins; Time Factors; Trachea

Topics: Analysis of Variance; Anaphylaxis; Animals; Antigen-Antibody Reactions; Benzyl Compounds; Carbon Radioisotopes; Cyclic AMP; Cyclic GMP; Ethylenediamines; Guinea Pigs; Histamine; Histamine H1 Antagonists; Humans; Imidazoles; In Vitro Techniques; Iodine Radioisotopes; Lung; Ovalbumin; Pyridines; Rabbits; Radioimmunoassay; Thiourea; Tritium

Topics: Anaphylaxis; Animals; Histamine H1 Antagonists; Hypotension; Indomethacin; Injections, Intravenous; Kinins; Ovalbumin; Promethazine; Prostaglandin Antagonists; Prostaglandins; Rats; Serotonin Antagonists

Topics: Anaphylaxis; Animals; Antibodies; Antigens; Cattle; Cattle Diseases; Freund's Adjuvant; Hemagglutination Tests; Immunodiffusion; Injections, Intravenous; Injections, Subcutaneous; Ovalbumin; Passive Cutaneous Anaphylaxis

Topics: Aminobenzoates; Anaphylaxis; Animals; Arthus Reaction; Ascitic Fluid; B-Lymphocytes; Cyclophosphamide; Guinea Pigs; Hypersensitivity, Delayed; Immunization, Passive; Immunosuppression Therapy; Ovalbumin; Skin Tests; Spleen; Transplantation, Homologous

Topics: Anaphylaxis; Animals; Ascitic Fluid; Bucladesine; Cromolyn Sodium; Cytoplasmic Granules; Immune Sera; Indomethacin; Isoproterenol; Male; Mast Cells; Ovalbumin; Passive Cutaneous Anaphylaxis; Prostaglandins; Rats; Theophylline

Topics: Adenosine Triphosphate; Aminophylline; Anaphylaxis; Animals; Bordetella pertussis; Bucladesine; Cromolyn Sodium; Cytoplasmic Granules; Guinea Pigs; Ileum; Imidazoles; Immunization; Isoproterenol; Male; Mast Cells; Muscle Contraction; Muscle, Smooth; Norepinephrine; Nucleotides, Cyclic; Ovalbumin; p-Methoxy-N-methylphenethylamine; Papaverine; Phosphodiesterase Inhibitors; Phospholipases; Prostaglandins; Rats

Topics: Aluminum Hydroxide; Analysis of Variance; Anaphylaxis; Animals; Antibody Specificity; Asthma; Bordetella pertussis; Bronchial Spasm; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Immunization; Immunoglobulin E; Immunoglobulin G; Lung; Ovalbumin; Passive Cutaneous Anaphylaxis; Pressure; Rats; Rodent Diseases; Time Factors

Topics: Aluminum Hydroxide; Anaphylaxis; Animals; Atropine; Bordetella pertussis; Bronchial Spasm; Cromolyn Sodium; Dexamethasone; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Indomethacin; Isoproterenol; Mecamylamine; Methysergide; Ovalbumin; Pressure; Propranolol; Rats; Time Factors; Trachea; Vagotomy; Vagus Nerve

Topics: Anaphylaxis; Animals; Biological Transport, Active; Calcium; Electrophysiology; Guinea Pigs; Heart; Heart Atria; Heart Block; Heart Rate; Histamine; Immunization; In Vitro Techniques; Microelectrodes; Myocardium; Ovalbumin; Perfusion; Sodium; Verapamil

Topics: Anaphylaxis; Animals; Blood Pressure; Central Venous Pressure; Female; Guinea Pigs; Heart Rate; Hematocrit; Histamine; Hydrogen-Ion Concentration; Male; Ovalbumin

Topics: Anaphylaxis; Animals; Antibody Formation; Cattle; Cattle Diseases; Chickens; Gastrointestinal Motility; Horses; Immune Sera; Injections, Intravenous; Lung; Lung Diseases; Lymph Nodes; Ovalbumin; Pulmonary Edema; Pulmonary Emphysema; Respiratory Insufficiency; Salivation; Sheep; Sheep Diseases; Tears

Topics: Aerosols; Anaphylaxis; Animals; Antigens; Bronchi; Carbon Radioisotopes; Chromatography, Thin Layer; Constriction; Depression, Chemical; Guinea Pigs; Histamine; Indomethacin; Male; Ovalbumin; Pharmaceutical Vehicles; Prostaglandins; Respiration; Stimulation, Chemical; Time Factors; Tritium

Topics: Acute Disease; Anaphylaxis; Animals; Apnea; Carotid Arteries; Erythrocyte Count; Hemodynamics; Histamine; Hypersensitivity, Immediate; Hypertension; Hypertension, Pulmonary; Leukocyte Count; Leukopenia; Ovalbumin; Swine; Swine Diseases; Thrombocytopenia

Topics: Anaphylaxis; Animals; Antigens; Butyrates; Cromolyn Sodium; Cyclic AMP; Epinephrine; Guinea Pigs; Histamine; Histamine Release; Lung; Norepinephrine; Ovalbumin

Topics: Anaphylaxis; Antibody Formation; Antigens; Calcium; Cations, Divalent; Histamine Release; Immunoglobulin E; Mast Cells; Ovalbumin; Phosphatidylcholines; Phospholipids; Strontium

Topics: Anaphylaxis; Animals; Antigens; Atropine; Guinea Pigs; Histamine; Histamine Release; Ileum; Male; Muscle Contraction; Muscle, Smooth; Ovalbumin; Prostaglandins; SRS-A; Tritium

Topics: Anaphylaxis; Animals; Biological Assay; Culture Techniques; Cytological Techniques; Guinea Pigs; Histamine; Histamine Release; Hyaluronoglucosaminidase; Male; Mast Cells; Mesentery; Microbial Collagenase; Ovalbumin

Topics: Anaphylaxis; Animals; Antigens, Bacterial; Bordetella pertussis; Cromolyn Sodium; Dose-Response Relationship, Drug; Eye; Guinea Pigs; Histamine Release; Hot Temperature; Hypersensitivity; Immune Sera; Immunization; Immunoglobulin E; Isoantibodies; Lung; Male; Mercaptoethanol; Ovalbumin; Passive Cutaneous Anaphylaxis

Topics: Anaphylaxis; Animals; Cross Reactions; Depression, Chemical; Epinephrine; Guinea Pigs; Haplorhini; Histamine Release; Immune Sera; Lung; Norepinephrine; Ovalbumin; Perfusion; Prostaglandins; Pulmonary Veins; Radioimmunoassay

Topics: Anaphylaxis; Animals; Cromolyn Sodium; Cyclic AMP; Epinephrine; Guinea Pigs; Histamine Release; Immunization; In Vitro Techniques; Isoproterenol; Lung; Norepinephrine; Ovalbumin; Tritium

1. Anaphylaxis was induced in the isolated heart of the guinea-pig in the presence of burimamide at concentrations of 4 x 10(-5)M and 2.7 x 10(-4)M.2. Burimamide did not affect the immunological release of histamine; however, it selectively antagonized the positive inotropic and chronotropic effects of released histamine. The antagonism of the positive chronotropic effect was concentration-dependent.3. Neither the negative dromotropic effect nor the decrease in coronary flow rate occurring during anaphylaxis were inhibited by burimamide.4. The results are in agreement with the double histamine receptor theory and suggest that, in the heart of the guinea-pig, H(2)-receptors are involved in the positive inotropic and chronotropic effects of released histamine, and H(1)-receptors in the negative dromotropic effect.

Topics: Anaphylaxis; Animals; Antigens; Electrocardiography; Guinea Pigs; Heart; Heart Rate; Histamine H1 Antagonists; Histamine Release; Imidazoles; In Vitro Techniques; Ovalbumin; Receptors, Drug; Thiourea; Time Factors; Transducers

Topics: Anaphylaxis; Animals; Antigens; Guinea Pigs; Heparin; Histamine; Histamine H1 Antagonists; Liver; Ovalbumin; Tissue Extracts

Topics: Anaphylaxis; Animals; Antigens; Benzyl Compounds; Chromatography, Ion Exchange; Dose-Response Relationship, Drug; Epinephrine; Ethylenediamines; Guinea Pigs; Histamine; Histamine H1 Antagonists; Norepinephrine; Ovalbumin; Pyridines; Shock, Septic; Toxins, Biological

Topics: Anaphylaxis; Animals; Antigen-Antibody Complex; Antilymphocyte Serum; Blood; Horses; Immunodiffusion; Immunoglobulin E; Immunoglobulin G; Immunoglobulin M; Immunosuppression Therapy; Iodine Isotopes; Mercaptoethanol; Mice; Mice, Inbred AKR; Ovalbumin; Precancerous Conditions; Rabbits

Topics: Anaphylaxis; Animals; Antibodies; Antigens; Butylamines; Carboxylic Acids; Cromolyn Sodium; Dinitrophenols; Ethanolamines; Immunity, Cellular; Mast Cells; Ovalbumin; Passive Cutaneous Anaphylaxis; Phenethylamines; Pyrimidines; Rats; Theophylline; Tritium; Xanthenes

1. Human lung tissue, passively sensitized with reaginic antibodies, released prostaglandins E(1), E(2) and F(2alpha) in addition to histamine and slow reacting substance (SRS-A), when exposed to the appropriate antigen. No rabbit aorta contracting substance (RCS) was detected.2. Experiments with rats and guinea-pigs showed that the release of RCS is not confined to anaphylactic reactions mediated by non-reaginic antibodies but may be a feature of anaphylaxis in guinea-pigs alone.3. Human lung tissue gently agitated with a blunt nylon rod liberated an E-type prostaglandin and RCS in addition to histamine and SRS-A.4. Human isolated bronchial muscle was contracted by RCS.5. Disodium cromoglycate antagonized the release of prostaglandins during anaphylaxis but not during agitation of human lung tissue, whereas indomethacin blocked the release of prostaglandins during agitation and anaphylaxis.6. The release of an E-type prostaglandin during anaphylaxis in human lung tissue, which inhibits the further release of histamine could be another example of the regulatory role of prostaglandins in body functions.

Topics: Anaphylaxis; Animals; Aorta; Bordetella pertussis; Bronchi; Cromolyn Sodium; Histamine; Humans; Immunoglobulin E; In Vitro Techniques; Indomethacin; Lung; Muscle Contraction; Muscle, Smooth; Ovalbumin; Prostaglandins; Rabbits; Rats; Spasm; SRS-A; Tissue Extracts

Topics: Acetamides; Anaphylaxis; Animals; Cyclic AMP; Freund's Adjuvant; Germ-Free Life; Guinea Pigs; Immune Sera; Immunoglobulin E; Lung; Mice; Ovalbumin; Passive Cutaneous Anaphylaxis; Pertussis Vaccine; Phosphodiesterase Inhibitors; Precipitins; Pyrazines; Pyrimidines; Rats; Triazoles

Topics: Adrenal Glands; Age Factors; Anaphylaxis; Animals; Bordetella pertussis; Drug Hypersensitivity; Female; Histamine; Hot Temperature; Humans; Hydrogen-Ion Concentration; Immunization; Injections, Intraperitoneal; Injections, Intravenous; Injections, Subcutaneous; Leukocyte Count; Mice; Mice, Inbred BALB C; Mice, Inbred CBA; Ovalbumin; Propionibacterium acnes; Serotonin

Topics: Anaphylaxis; Animals; Antigen-Antibody Reactions; Capillary Permeability; Carbon; Chemotaxis; Complement System Proteins; Eosinophilia; Fluorescent Antibody Technique; Guinea Pigs; Hypersensitivity, Immediate; Immune Sera; Immunoglobulin E; Immunoglobulin G; Inflammation; Leukocytosis; Mast Cells; Neutrophils; Ovalbumin; Phagocytosis; Proteins; Skin

Topics: Anaphylaxis; Animals; Antigens; Female; Hookworm Infections; Immunoglobulin E; Injections, Intradermal; Ovalbumin; p-Methoxy-N-methylphenethylamine; Rats; Skin; Skin Tests

Topics: Acetylcholine; Aerosols; Airway Resistance; Anaphylaxis; Animals; Bronchi; Dose-Response Relationship, Drug; Female; Guinea Pigs; Histamine; Injections, Intramuscular; Lung; Lung Compliance; Ovalbumin; Propranolol; Respiratory System; Spirometry

Topics: Anaphylaxis; Animals; Antibody Formation; Cattle; Diphenhydramine; Epinephrine; Hemagglutination Tests; Immune Sera; Immunity, Maternally-Acquired; Iodine Isotopes; Ovalbumin; Pancreas; Rabbits; Ribonucleases; Serum Albumin, Bovine

Topics: Age Factors; Anaphylaxis; Animals; Arthritis, Rheumatoid; Freund's Adjuvant; Ovalbumin; Prostaglandins; Rabbits; Species Specificity; Synovial Fluid

Topics: Aerosols; Anaphylaxis; Animals; Antigens; Desensitization, Immunologic; Glucuronidase; Guinea Pigs; Horses; Hyaluronoglucosaminidase; Immune Tolerance; Immunization, Secondary; Male; Mice; Ovalbumin; Rats; Staining and Labeling

Topics: Aerosols; Ammonium Sulfate; Anaphylaxis; Animals; Desensitization, Immunologic; Freezing; gamma-Globulins; Guinea Pigs; Hot Temperature; Hydrogen-Ion Concentration; Immune Sera; Immunity, Maternally-Acquired; Immunization, Secondary; Immunoelectrophoresis; Injections, Intraperitoneal; Injections, Intravenous; Ovalbumin; Time Factors

Topics: Anaphylaxis; Animals; Antigens; Cardiovascular Diseases; Chickens; Diethylcarbamazine; Freund's Adjuvant; Muscle, Smooth; Ovalbumin; Rats; SRS-A

Topics: Anaphylaxis; Animals; Antigen-Antibody Reactions; Cattle; Histamine Release; Horses; Immune Sera; Lung; Male; Ovalbumin; p-Methoxy-N-methylphenethylamine; Serotonin

1. Anaphylactic histamine release from rat peritoneal mast cells is dependent on the presence of calcium ions. Graded increase of histamine release occurs as the calcium ion concentration is raised from 0.1 to 1.0 m-mole/l.2. Magnesium antagonizes the effect of calcium. The dissociation constant of the Mg-receptor complex was found to be 9.4 m-mole/l.3. Strontium will replace calcium ions in the activation of anaphylactic histamine release. Graded increase of histamine release occurs when the strontium ion concentration is raised from 1.0 to 10.0 m-mole/l.4. Magnesium also antagonizes the effect of strontium. The dissociation constant of the magnesium-receptor complex was found to be 11.0 m-mole/l.5. The log concentration-effect curve for strontium has a greater maximum and steeper slope than the curve for calcium.6. Measurements of the interaction of calcium and strontium ions are in agreement with the hypothesis that strontium possesses a higher efficacy but a lower affinity than calcium, for the ;calcium receptor' in mast cells.7. Barium will replace calcium in the activation of anaphylactic histamine release.

Topics: Anaphylaxis; Animals; Ascitic Fluid; Barium; Calcium; Female; Histamine Release; In Vitro Techniques; Magnesium; Male; Mast Cells; Ovalbumin; Rats; Receptors, Drug; Stimulation, Chemical; Strontium

Topics: Airway Resistance; Anaphylaxis; Animals; Antigens; Atropine; Autacoids; Desensitization, Immunologic; Guinea Pigs; Histamine H1 Antagonists; Histamine Release; Ileum; Kallikreins; Lung; Muscle Contraction; Muscle, Smooth; Ovalbumin; Prostaglandins

Topics: Anaphylaxis; Animals; Antigens; Freund's Adjuvant; Guinea Pigs; Histamine Release; Immune Sera; Immunity, Maternally-Acquired; In Vitro Techniques; Intestine, Small; Male; Ovalbumin; Precipitin Tests; Rabbits; Serotonin; Spectrophotometry

Topics: Aerosols; Airway Resistance; Anaphylaxis; Animals; Antigen-Antibody Reactions; Carbachol; Guinea Pigs; Histamine; Histamine Release; Injections, Intraperitoneal; Injections, Intravenous; Injections, Subcutaneous; Male; Ovalbumin; Phloretin; Prostaglandin Antagonists; SRS-A; Statistics as Topic

Topics: 5-Hydroxytryptophan; Anaphylaxis; Animals; Antigens; Bordetella pertussis; Carboxy-Lyases; Intestine, Small; Liver; Lung; Monoamine Oxidase; Ovalbumin; Pyloric Antrum; Rats; Serotonin; Skin; Tryptophan Synthase

Topics: Anaphylaxis; Animals; Antigens; Female; Guinea Pigs; Histamine; Histamine H1 Antagonists; Lung; Male; Ovalbumin; Premedication; Time Factors

Topics: Anaphylaxis; Animals; Antigens; Benzyl Compounds; Bromine; Dioxoles; Dose-Response Relationship, Drug; Ethylamines; Ethylenediamines; Female; Guinea Pigs; Histamine H1 Antagonists; Lactones; Male; Ovalbumin; Papaverine; Parasympatholytics; Pyridines; Quinoxalines; Scopolamine; Styrenes

Topics: Acute Disease; Amidines; Anaphylaxis; Anesthesia, General; Animals; Antigens; Atropine; Blood Cell Count; Bradykinin; Cattle; Cattle Diseases; Female; Freund's Adjuvant; Histamine H1 Antagonists; Injections, Intravenous; ortho-Aminobenzoates; Ovalbumin; Phenylbutazone; Serotonin Antagonists; SRS-A; Toluene; Vagotomy

Topics: Anaphylaxis; Animals; Antigen-Antibody Reactions; Antigens; Atropine; Barium; Binding, Competitive; Chlorpheniramine; Colon; Depression, Chemical; Diphenhydramine; Epinephrine; Guinea Pigs; Histamine; Histamine H1 Antagonists; Immunodiffusion; In Vitro Techniques; Male; Muscle Contraction; Muscle, Smooth; Ovalbumin; Papaverine; Pyrimidines; Rabbits

Topics: Anaphylaxis; Animals; Antigens; Edema Disease of Swine; Escherichia coli; Intestines; Ovalbumin; Polysaccharides, Bacterial; Swine; Swine Diseases

Topics: Aerosols; Anaphylaxis; Animals; Antibodies; Antibody Formation; Antigens; Desensitization, Immunologic; Female; Freund's Adjuvant; Guinea Pigs; Hemagglutination Tests; Immunization; Male; Ovalbumin; Passive Cutaneous Anaphylaxis

Topics: Anaphylaxis; Animals; Antigen-Antibody Complex; Binding Sites; Cell Membrane; Complement System Proteins; Erythrocytes; Guinea Pigs; Humans; Immune Sera; Ovalbumin; Properdin; Rabbits; Toxins, Biological; Zymosan

Topics: Action Potentials; Anaphylaxis; Animals; Antigen-Antibody Reactions; Antigens; Cold Temperature; Desensitization, Immunologic; Electric Stimulation; Freund's Adjuvant; Guinea Pigs; Histamine; Hormones; Membrane Potentials; Membranes; Ovalbumin; Phrenic Nerve; Serum Albumin

Topics: Anaphylaxis; Animals; Bronchi; Centrifugation, Density Gradient; Guinea Pigs; Lung; Male; Microsomes; Mitochondria; Neuraminic Acids; Nitrogen; Ovalbumin; Perfusion; Phospholipids; Phosphorus; Proteins; Subcellular Fractions; Time Factors; Trachea

Topics: Anaphylaxis; Animals; Aorta; Autoradiography; Blood Cells; Epithelial Cells; Epithelium; Guinea Pigs; Injections, Intraperitoneal; Injections, Intravenous; Injections, Subcutaneous; Leukocyte Count; Mitosis; Ovalbumin; Tritium

Topics: Anaphylaxis; Animals; Antibodies; Chromatography, DEAE-Cellulose; Complement Fixation Tests; Electrophoresis; Female; Freund's Adjuvant; Guinea Pigs; Hemagglutination; Hemolysis; Immune Sera; Immunoelectrophoresis; Immunoglobulin G; Immunoglobulins; Ovalbumin; Precipitin Tests; Ultracentrifugation

Topics: Anaphylaxis; Animals; Antigens; Body Temperature; Cattle; Cattle Diseases; Female; Jugular Veins; Lymph; Lymphatic System; Ovalbumin; Rectum; Thoracic Duct; Time Factors

Topics: Anaphylaxis; Animals; Antibodies; Antigens; Female; Freund's Adjuvant; Guinea Pigs; Ileum; Injections, Intraperitoneal; Muscle Contraction; Muscle, Smooth; Ovalbumin; Time Factors

Topics: Adrenal Glands; Adrenalectomy; Anaphylaxis; Animals; Antibody Formation; Hypophysectomy; Hypothalamus; Male; Ovalbumin; Pertussis Vaccine; Pituitary Gland; Precipitin Tests; Rats

Topics: Anaphylaxis; Animals; Antigens; Desensitization, Immunologic; Dextrans; Epinephrine; Guinea Pigs; Histamine; Immunization; Mast Cells; Muscle Contraction; Norepinephrine; Ovalbumin; p-Methoxy-N-methylphenethylamine; Papillary Muscles; Peptides; Rats; Serotonin; Swine; Tachyphylaxis; Toxins, Biological

Topics: Amine Oxidase (Copper-Containing); Anaphylaxis; Antigens; Histamine; Histamine Release; Ileum; Liver; Lung; Ovalbumin

Topics: Anaphylaxis; Animals; Antigens; Catecholamines; Guinea Pigs; Histamine; Histamine Release; Humans; Immunity, Maternally-Acquired; Leukocytes; Lung; Mites; Ovalbumin; Sympathomimetics

Topics: Anaphylaxis; Animals; Antigens; Bronchial Spasm; Chickens; Histamine H1 Antagonists; Histamine Release; In Vitro Techniques; Lung; Muscle Contraction; Muscle, Smooth; Ovalbumin; Perfusion

Topics: Amine Oxidase (Copper-Containing); Anaphylaxis; Animals; Antigens; Carboxy-Lyases; Duodenum; Fluorometry; Glucocorticoids; Histamine; Histamine Release; Histidine; Intestine, Small; Liver; Lung; Mice; Ovalbumin; Pertussis Vaccine; Rats; Skin; Stomach

Topics: Anaphylaxis; Animals; Antigens; Blood; Cattle; Histamine Release; Horses; In Vitro Techniques; Lung; Ovalbumin; p-Methoxy-N-methylphenethylamine; Pulmonary Veins; Stimulation, Chemical

Topics: Air; Anaphylaxis; Animals; Aorta; Arachis; Blood Pressure; Dextrans; Drug Hypersensitivity; Emulsions; Female; Guinea Pigs; Histamine Release; Hypersensitivity; Iron-Dextran Complex; Lung; Male; Muscle Contraction; Oils; Ovalbumin; Perfusion; Polystyrenes; Pressure; Prostaglandins; Pulmonary Artery; Rabbits; Rats; Stimulation, Chemical; Suspensions; Time Factors

Topics: Adult; Anaphylaxis; Angioedema; Anhydrides; Animals; Antibodies; Antibody Formation; Antibody Specificity; Antigens; Aspirin; Carrier Proteins; Cattle; Drug Contamination; Drug Eruptions; Drug Hypersensitivity; Erythrocytes; Female; gamma-Globulins; Guinea Pigs; Haptens; Hemagglutination Tests; Humans; Hypersensitivity, Immediate; Immunodiffusion; Lysine; Male; Middle Aged; Ovalbumin; Passive Cutaneous Anaphylaxis; Serum Albumin; Skin Tests; Tannins; Urticaria

Topics: Alpha-Globulins; Anaphylaxis; Animals; Bradykinin; Endopeptidases; Female; Histamine; Kinins; Male; Ovalbumin; Pertussis Vaccine; Rats; Serotonin

Topics: Anaphylaxis; Animals; Aorta; Aspirin; Bronchial Spasm; Guinea Pigs; Histamine Release; Immunity, Cellular; Lung; Ovalbumin; Prostaglandins; Pulmonary Embolism; Rabbits; SRS-A

Topics: Anaphylaxis; Animals; Antibodies, Anti-Idiotypic; Cromolyn Sodium; Female; Histamine; Histamine Release; Hot Temperature; Immune Sera; Male; Ovalbumin; Rats; Skin

Topics: Anaphylaxis; Animals; Antibodies; Germ-Free Life; Guinea Pigs; Histamine H1 Antagonists; Immune Sera; Immunization, Passive; Ovalbumin; Propranolol

Topics: Adjuvants, Immunologic; Anaphylaxis; Animals; Antigens; Bacillus subtilis; Bordetella pertussis; Immunization; Immunodiffusion; Immunoglobulin E; Mice; Ovalbumin; Passive Cutaneous Anaphylaxis; Peptide Hydrolases; Precipitins

Topics: Anaphylaxis; Animals; Antigens; Lung; Male; Muscle Spindles; Nerve Fibers, Myelinated; Neural Conduction; Neurons; Neurons, Afferent; Ovalbumin; Rabbits; Respiration; Respiration, Artificial; Synaptic Transmission; Vagotomy; Vagus Nerve

Topics: Aerosols; Anaphylaxis; Animals; Blood Pressure; Bronchi; Bronchial Spasm; Bronchodilator Agents; Cats; Constriction; Guinea Pigs; Heart Rate; Histamine H1 Antagonists; In Vitro Techniques; Isoproterenol; Metaproterenol; Muscle, Smooth; Nictitating Membrane; Ovalbumin; Serotonin Antagonists; Trachea

Topics: Absorption; Anaphylaxis; Animals; Antibodies; Antibody Formation; Antigen-Antibody Complex; Blood Proteins; Complement System Proteins; Dextrans; Erythrocytes; Glycogen; Hemagglutination Tests; Hemolytic Plaque Technique; Ileum; Immune Sera; Immunoelectrophoresis; Muscle Contraction; Nitrogen; Ovalbumin; Peptides; Rats; Tachyphylaxis; Toxins, Biological; Zymosan

Topics: Amine Oxidase (Copper-Containing); Anaphylaxis; Animals; Antigens; Female; Guinea Pigs; Heparin; Histamine; Immunization; Liver; Male; Metyrapone; Ovalbumin; Papaverine

Topics: Anaphylaxis; Animals; Antigens; Guinea Pigs; Ileum; Immunoelectrophoresis; Immunoglobulin G; Immunoglobulins; Mice; Ovalbumin; Papain; Passive Cutaneous Anaphylaxis; Peptides; Rabbits

Topics: Acetylcholine; Anaphylaxis; Animals; Antibodies; Antigen-Antibody Reactions; Antigens; Barium; Bradykinin; Colon; Culture Media; Guinea Pigs; Histamine; Immunity, Maternally-Acquired; In Vitro Techniques; Male; Membrane Potentials; Muscle Contraction; Muscle, Smooth; Ovalbumin; Potassium; Precipitin Tests

Topics: Anaphylaxis; Animals; Bronchial Spasm; Coronary Vessels; Dexamethasone; Esophageal Achalasia; Female; Guinea Pigs; Heart; Heart Rate; Histamine; In Vitro Techniques; Male; Muscle Contraction; Ovalbumin; Perfusion; Pulmonary Circulation; Vascular Resistance

1. The mast-cell distribution in the various layers of the ileum has been described.2. Histamine-content, anaphylactic histamine-release and the anaphylactic dose-response curve of the full-thickness ileum and of the longitudinal muscle strip have been measured and compared.3. Tetrodotoxin 10(-7) g/ml had no obvious effect on the anaphylactic dose-response curve of either preparation. This suggests that the plexus is not of any great importance in the Schultz-Dale reaction.4. Exposure of the longitudinal muscle strip to octylamine 10(-3) g/ml for 1 min reduced the mast cell content by 95-100%. After this treatment the dose-response curve to antigen was eliminated, although the muscle still responded to small doses of histamine and to anaphylactic mediators. Pretreatment of antibody with octylamine did not impair passive sensitization and subsequent response to antigenic challenge. This suggests that the classical Schultz-Dale reaction in the strip is mediated mainly by mast cells, and possibly other cells, and is probably not due to a direct effect of the antigen-antibody reaction on the smooth muscle.5. The typical three-phase anaphylactic response (quick contraction, quick relaxation, slow contraction) of full-thickness ileum is discussed and compared with the predominantly two-phase response of the longitudinal muscle strip. No evidence was found for the release of a relaxation-factor. It is suggested that the initial fast phase may be due to mediators released from mast cells among the longitudinal muscle fibres, and the sustained contraction to a second wave of mediators reaching the longitudinal muscle from deeper layers of the ileum.

Topics: Amines; Anaphylaxis; Animals; Antigens; Dinitrophenols; Guinea Pigs; Histamine; Histamine Release; Humans; Ileum; In Vitro Techniques; Mast Cells; Muscle, Smooth; Myenteric Plexus; Ovalbumin; Serum Albumin; Tetrodotoxin

Topics: Amine Oxidase (Copper-Containing); Amines; Anaphylaxis; Animals; Antigens; Blood Coagulation Tests; Drug Antagonism; Guanidines; Guinea Pigs; Heparin; Histamine; Histamine H1 Antagonists; Histamine Release; Injections, Intraperitoneal; Ovalbumin; Papaverine; Pyrroles

Topics: Amidines; Anaphylaxis; Animals; Dextrans; Emphysema; Female; Guinea Pigs; Hematocrit; Histamine; Histamine Release; Immune Sera; Immunization; Male; Ovalbumin; Peptides; Pyridines; Tachyphylaxis; Toxins, Biological

Topics: Amine Oxidase (Copper-Containing); Anaphylaxis; Animals; Antigens; Female; Guinea Pigs; Heparin; Histamine; Histamine Release; Immunization; Liver; Male; Ovalbumin; Peptides; Toxins, Biological

Topics: Anaphylaxis; Animals; Antigen-Antibody Reactions; Antigens; gamma-Globulins; Guinea Pigs; Histamine Release; Ileum; Immune Sera; Muscle Contraction; Ovalbumin

Topics: Anaphylaxis; Animals; Antigens; Benzopyrans; Dinitrophenols; Ferritins; Haplorhini; Histamine H1 Antagonists; Histamine Release; Humans; Hypersensitivity, Immediate; Immunity, Active; Immunity, Maternally-Acquired; Immunoglobulin E; Leukocytes; Lung; Ovalbumin; Rabbits; Rhinitis, Allergic, Seasonal; Skin Tests

Topics: Amines; Anaphylaxis; Anesthesia, Intravenous; Animals; Blood Pressure; Bronchi; Consciousness; Dyspnea; Female; Histamine H1 Antagonists; Histamine Release; Male; Methysergide; Ovalbumin; p-Methoxy-N-methylphenethylamine; Polymyxins; Pulmonary Circulation; Sheep; Trachea

Topics: Anaphylaxis; Animals; Antibodies; Antibody Formation; Antigens; Dinitrophenols; Female; Haptens; Histamine Release; Immunoglobulin E; Mast Cells; Maternal-Fetal Exchange; Mice; Milk; Ovalbumin; Passive Cutaneous Anaphylaxis; Pregnancy; Serum Albumin, Bovine

Topics: Anaphylaxis; Animals; Antibodies; Dinitrophenols; Disease Models, Animal; Histamine Release; Immunoglobulin E; In Vitro Techniques; Mast Cells; Mice; Ovalbumin; Passive Cutaneous Anaphylaxis; Peritoneum; Serum Albumin, Bovine

Topics: Anaphylaxis; Animals; Blood Pressure; Electrocardiography; Heart; Heart Conduction System; Ovalbumin; Rats

Topics: Anaphylaxis; Animals; Antigen-Antibody Reactions; Heart Conduction System; In Vitro Techniques; Myocardium; Ovalbumin; Perfusion; Rats

Topics: Amine Oxidase (Copper-Containing); Anaphylaxis; Animals; Guinea Pigs; Histamine; Liver; Ovalbumin

Topics: Adrenalectomy; Anaphylaxis; Animals; Bronchial Spasm; Catecholamines; Guinea Pigs; Histamine; Histamine H1 Antagonists; Immunization; Lung; Ovalbumin; Pyridines; Pyrroles; Reserpine; Sympatholytics; Urethane

Topics: Anaphylaxis; Animals; Antibody Formation; Azo Compounds; Haptens; Molecular Weight; Ovalbumin; Rabbits; Streptococcus pneumoniae

Topics: Anaphylaxis; Animals; Cardiac Output; Coronary Vessels; Guinea Pigs; Heart; Heart Block; Heart Rate; Histamine; Histamine H1 Antagonists; In Vitro Techniques; Myocardium; Ovalbumin; Oxygen Consumption; Papaverine; Perfusion; Pyrroles

Topics: Anaphylaxis; Animals; Arrhythmias, Cardiac; Asthma; Blood Pressure; Chloroform; Chloroquine; Dopamine; Electrocardiography; Female; Heart Rate; Histamine; Histamine H1 Antagonists; Lung; Male; Mice; Norepinephrine; Ovalbumin; Quinolines; Rabbits; Serotonin; Vascular Resistance

Topics: Anaphylaxis; Animals; Blood Pressure; Bronchial Spasm; Cardiac Output; Drug Synergism; Epinephrine; Female; Guinea Pigs; Heart Atria; Histamine; Histamine H1 Antagonists; Male; Ovalbumin; Papaverine; Pulmonary Artery; Pulmonary Circulation; Vascular Resistance

Topics: Adrenal Cortex Hormones; Aerosols; Anaphylaxis; Animals; Anti-Inflammatory Agents; Antigens; Benzyl Compounds; Betamethasone; Bronchi; Cortisone; Dexamethasone; Drug Hypersensitivity; Female; Fludrocortisone; Guinea Pigs; Hydrocortisone; Methylamines; Ovalbumin; Paramethasone; Prednisolone; Pyridines; Time Factors; Triamcinolone

Topics: Anaphylaxis; Animals; Antibodies; Antigens; Colostrum; Digestive System; Escherichia coli Infections; Female; Hypersensitivity, Immediate; Immunization, Passive; Liver; Lung; Maternal-Fetal Exchange; Myocardium; Ovalbumin; Pregnancy; Skin Tests; Swine; Swine Diseases

Topics: Anaphylaxis; Animals; Anti-Inflammatory Agents; Bromine; Guinea Pigs; Imipramine; Ketones; Ovalbumin; Quinazolines; Terpenes

Topics: Anaphylaxis; Animals; Antigen-Antibody Reactions; Blood Coagulation; Fibrinogen; In Vitro Techniques; Ovalbumin; Rabbits; Thrombelastography

Topics: Anaphylaxis; Animals; Antigens; Desensitization, Immunologic; Guinea Pigs; Histamine; Ileum; Male; Muscle Contraction; Muscle, Smooth; Ovalbumin

Topics: Aerosols; Anaphylaxis; Animals; Antigens; Female; Guinea Pigs; Hemagglutination Tests; Injections, Intraperitoneal; Nitrogen Dioxide; Ovalbumin; Ozone; Passive Cutaneous Anaphylaxis; Respiratory Hypersensitivity; Serum Albumin; Skin Tests; Sulfur Dioxide

Topics: Anaphylaxis; Animals; Antibodies; Antigens; Biphenyl Compounds; Guinea Pigs; Hemagglutination Tests; Hot Temperature; Ovalbumin

Topics: Anaphylaxis; Animals; Capillary Permeability; Chlorides; Corticosterone; Depression, Chemical; Diuresis; Dogs; Edema; Female; Glycosides; Guinea Pigs; Injections, Intravenous; Male; Mice; Ovalbumin; Plants, Medicinal; Potassium; Rabbits; Rats; Sodium; Solubility; Species Specificity; Stimulation, Chemical; Terpenes

Topics: Adjuvants, Immunologic; Anaphylaxis; Animals; Antibody Formation; Antigens; Complement Fixation Tests; Freund's Adjuvant; Guinea Pigs; Hemagglutination Tests; Immunoelectrophoresis; Ovalbumin

Topics: Albumins; Anaphylaxis; Animals; Bronchi; Cattle; Histamine; In Vitro Techniques; Muscle, Smooth; Ovalbumin; Plasma; Pulmonary Artery; Pulmonary Veins; Serotonin

Topics: Albumins; Anaphylaxis; Animals; Bronchi; Cattle; Histamine; In Vitro Techniques; Muscle, Smooth; Ovalbumin; Plasma; Pulmonary Artery; Pulmonary Veins; Serotonin

Topics: Anaphylaxis; Animals; Antibodies; Antigen-Antibody Reactions; Chlordiazepoxide; Desensitization, Immunologic; Diphtheria Toxoid; Female; Guinea Pigs; Hemolysin Proteins; Hypersensitivity, Delayed; Injections, Intradermal; Injections, Intraperitoneal; Injections, Intravenous; Male; Methods; Ovalbumin; Rats; Serum Albumin, Bovine; Skin Tests; Time Factors

Topics: Adjuvants, Immunologic; Anaphylaxis; Animals; Antibodies; Antigens; Cytoplasmic Granules; Dinitrophenols; Hemocyanins; Immune Sera; Immunoglobulin E; Immunoglobulin G; Mast Cells; Mice; Ovalbumin; Passive Cutaneous Anaphylaxis

Topics: Anaphylaxis; Animals; Antigen-Antibody Reactions; Antigens; Chloroquine; Chromatography, Gel; Female; Guinea Pigs; Immune Sera; Immunization; Immunization, Secondary; Molecular Weight; Ovalbumin; Skin Tests

Topics: Anaphylaxis; Animals; Cat Diseases; Cats; Fibrinogen; Freund's Adjuvant; gamma-Globulins; Hypersensitivity; Ovalbumin; Serum Albumin, Bovine

Topics: Anaphylaxis; Animals; Antigens; Carbon Dioxide; Cardiac Output; Ovalbumin; Oxygen; Oxygen Consumption; Partial Pressure; Rabbits

Topics: Aerosols; Alpha-Globulins; Anaphylaxis; Animals; Antigens; Beta-Globulins; Desensitization, Immunologic; Guinea Pigs; Humans; Immunity, Maternally-Acquired; Injections, Intravenous; Ovalbumin; Rabbits

Topics: Anaphylaxis; Animals; Arteries; Carbon Dioxide; Female; Hydrogen-Ion Concentration; Male; Nitrogen; Ovalbumin; Oxygen; Perfusion; Pulmonary Alveoli; Rabbits; Respiration; Time Factors; Vagotomy; Vagus Nerve; Veins

Topics: Anaphylaxis; Animals; Blood Pressure; Bradycardia; Femoral Artery; Heart Rate; Heart Ventricles; Hemodynamics; Hypotension; Ovalbumin; Rats

Topics: Aerosols; Alpha-Globulins; Anaphylaxis; Animals; Antigens; Beta-Globulins; Desensitization, Immunologic; Freezing; Guinea Pigs; Hot Temperature; Humans; Immunity, Maternally-Acquired; Injections, Intravenous; Ovalbumin

Topics: Aldehydes; Anaphylaxis; Animals; Antigens; Chickens; Cyanides; Fluorescent Antibody Technique; Freeze Drying; Guinea Pigs; Histological Techniques; Immunity, Maternally-Acquired; Indicators and Reagents; Lung; Lymph Nodes; Ovalbumin; Rabbits; Staining and Labeling

Topics: Anaphylaxis; Animals; Cardiovascular Diseases; Desensitization, Immunologic; Dextrans; Emphysema; Guinea Pigs; Histamine H1 Antagonists; Immune Sera; Ovalbumin; Tachyphylaxis

Topics: Anaphylaxis; Animals; Bronchial Spasm; Guinea Pigs; Heart; Histamine; Histamine H1 Antagonists; Hypersensitivity, Immediate; Hypoxia; In Vitro Techniques; Lung; Myocardium; Ovalbumin; Pyridines

Topics: Anaphylaxis; Animals; Anti-Inflammatory Agents; Aorta; Aspirin; Autacoids; Biological Assay; Drug Antagonism; Guinea Pigs; Histamine; Lung; Mefenamic Acid; Muscle Contraction; Ovalbumin; Perfusion; Prostaglandins; Rabbits

Topics: Anaphylaxis; Animals; Bronchial Spasm; Guinea Pigs; Histamine H1 Antagonists; Ischemia; Lung; Myocardium; Ovalbumin

Topics: Anaphylaxis; Animals; Antigen-Antibody Reactions; Aorta; Blood Pressure; Calcium Chloride; Cardiac Output; Cardiovascular Diseases; Female; Guinea Pigs; Heart; Heart Rate; Heart-Lung Machine; Hexobarbital; Histamine; Histamine H1 Antagonists; Male; Norepinephrine; Ovalbumin; Pyridines; Quinidine; Reserpine; Tyramine

Topics: Anaphylaxis; Animals; Female; Guinea Pigs; Haptens; Hemoglobins; Histamine; Histamine H1 Antagonists; Hyperkalemia; Isotonic Solutions; Male; Ovalbumin; Potassium; Potassium Chloride; Shock; Sodium Chloride

Topics: Amine Oxidase (Copper-Containing); Anaphylaxis; Animals; Antigens; Female; Guinea Pigs; Heparin; Liver; Male; Ovalbumin; Protamines; Sodium Chloride

Topics: Anaphylaxis; Animals; Cardiomyopathies; Guinea Pigs; Myocardium; Ovalbumin

Topics: Anaphylaxis; Animals; Antibodies; Guinea Pigs; Hypothalamus; Immunity; Injections, Intraperitoneal; Ovalbumin; Rats; Species Specificity

Topics: Adenosine Triphosphate; Aerosols; Aldehyde-Lyases; Anaphylaxis; Animals; Antigens; Glycolysis; Guinea Pigs; Hexosephosphates; Hypersensitivity; L-Lactate Dehydrogenase; Lung; Mitochondria; Ovalbumin; Time Factors

Topics: Anaphylaxis; Animals; Antibodies, Anti-Idiotypic; Female; Guinea Pigs; Ileum; Immune Sera; In Vitro Techniques; Male; Muscle Contraction; Muscle, Smooth; Ovalbumin; Stimulation, Chemical

Topics: Abomasum; Anaphylaxis; Animals; Antibody Formation; Cattle; Cattle Diseases; Digestive System; Edema; Hyperemia; Intestine, Small; Lung; Ovalbumin; Pulmonary Edema; Pulmonary Emphysema

Topics: Anaphylaxis; Animals; Antigen-Antibody Reactions; Antigens; Cold Temperature; Desensitization, Immunologic; Guinea Pigs; Ileum; In Vitro Techniques; Male; Muscle Contraction; Ovalbumin; Time Factors

Topics: Anaphylaxis; Animals; Anti-Inflammatory Agents; Blood Cell Count; Blood Platelets; Body Weight; Bone Marrow Diseases; Bone Marrow Examination; Fibrous Dysplasia of Bone; Hemoglobinometry; Leukocyte Count; Liver; Ovalbumin; Oxyphenbutazone; Phenylbutazone; Prednisolone; Pyrazoles; Rabbits; Reticulocytes; Spleen

Topics: Anaphylaxis; Animals; Antibody Formation; Antigen-Antibody Reactions; Antigens; Female; Intestine, Small; Iodine Isotopes; Liver; Lung; Male; Mice; Myocardium; Ovalbumin; Rats; Skin; Spleen

Topics: Anaphylaxis; Animals; Glucose; Hexoses; Injections, Intravenous; Ovalbumin; Rabbits; Rats

Topics: Aerosols; Allergens; Anaphylaxis; Animals; Antigens; Desensitization, Immunologic; Guinea Pigs; Ovalbumin

Topics: Albumins; Anaphylaxis; Anesthesia, General; Animals; Blood Pressure; Carotid Arteries; Cattle; Immune Sera; Ovalbumin; Pentobarbital; Respiratory System

Topics: Adjuvants, Immunologic; Anaphylaxis; Animals; Antigens; Blood Platelets; Ovalbumin; Pertussis Vaccine; Rabbits; Rats

Topics: Anaphylaxis; Animals; Asthma; Guinea Pigs; Neurons, Afferent; Ovalbumin; Pressoreceptors; Pulmonary Atelectasis; Pulmonary Emphysema; Reflex; Respiration; Vagus Nerve

Topics: Acetates; Anaphylaxis; Animals; Calcinosis; Depression, Chemical; Edema; Exudates and Transudates; Female; Hindlimb; Hypercalcemia; Lead; Ovalbumin; Phosphorus; Rats; Sodium Salicylate; Time Factors

Topics: Anaphylaxis; Animals; Depression, Chemical; Ovalbumin; Peptides; Rats; Toxins, Biological

Topics: Albinism; Anaphylaxis; Animals; Antibodies; Genes; Hybridization, Genetic; Inbreeding; Injections, Intravenous; Mice; Ovalbumin; Phenotype; Species Specificity

Topics: Anaphylaxis; Animals; Blood Pressure; Egg White; Glucose; Hexoses; Injections, Intravenous; Ovalbumin; Rats

Topics: Amine Oxidase (Copper-Containing); Anaphylaxis; Animals; Female; Guanidines; Guinea Pigs; Histamine Release; Liver; Lung; Male; Ovalbumin

Topics: Anaphylaxis; Animals; Blood Pressure; Kinins; Ovalbumin; Rats; Time Factors

Topics: Anaphylaxis; Animals; Antibody Formation; Basophils; Bone Marrow; Edetic Acid; Guinea Pigs; Histamine; Histamine Release; Ileum; In Vitro Techniques; Leukocyte Count; Lung; Ovalbumin; Time Factors

Topics: Anaphylaxis; Animals; Antibodies; Antigens; Desensitization, Immunologic; gamma-Globulins; Guinea Pigs; Hemagglutination; Ovalbumin; Rabbits; Serum Albumin, Bovine

Topics: Anaphylaxis; Animals; Basophils; Blood Chemical Analysis; Blood Platelets; Eosinophils; Female; Histamine; Histamine Release; In Vitro Techniques; Leukocyte Count; Leukocytes; Methods; Ovalbumin; Rabbits

Topics: Anaphylaxis; Animals; Calcium; Chloromercuribenzoates; Cysteine; Depression, Chemical; Female; Glutathione; Histamine Release; In Vitro Techniques; Iodoacetates; Leukocytes; Magnesium; Ovalbumin; Pyrroles; Rabbits; Stimulation, Chemical; Sulfites; Temperature; Thioglycolates

1. The sensitized guinea-pig uterus contracted on addition of antigen (egg-albumin), even after it had been completely depolarized in an isotonic potassium sulphate solution.2. The contractile response of the depolarized preparation started at a later time after addition of the antigen, and had a smaller amplitude, than the Schultz-Dale contraction induced in the ordinary Ringer solution.3. A contracting substance was released from the depolarized uterus. The average histamine equivalent of this substance was 89% of the histamine concentration which reproduced the anaphylactic contraction and probably proportional to the mechanical response.4. The main component of the material released from the uterus in the ordinary Ringer was histamine. The material released from the depolarized uterus did not contain any demonstrable histamine activity.

Topics: Anaphylaxis; Animals; Antigen-Antibody Reactions; Female; Guinea Pigs; Histamine Release; Muscle Contraction; Ovalbumin; Uterus

Topics: Action Potentials; Anaphylaxis; Animals; Antibodies; Antigen-Antibody Reactions; Arrhythmias, Cardiac; Bradycardia; Cardiac Complexes, Premature; Electrocardiography; Gastric Mucosa; Guinea Pigs; Heart; Heart Block; Heart Rate; Hypersensitivity, Delayed; In Vitro Techniques; Injections, Intravenous; Intestine, Small; Ischemia; Myocardium; Ovalbumin; Tachycardia; Wolff-Parkinson-White Syndrome

Topics: Anaphylaxis; Animals; Kallikreins; Kinins; Ovalbumin

Topics: Aminopyrine; Anaphylaxis; Animals; Aprotinin; Body Temperature; Bradykinin; Histamine H1 Antagonists; Injections, Intraperitoneal; Ovalbumin; Pertussis Vaccine; Phenylbutazone; Rats; Serotonin Antagonists

Topics: Acetylcholine; Aerosols; Anaphylaxis; Animals; Bradykinin; Bronchi; Bronchial Spasm; Chlordiazepoxide; Drug Antagonism; Guinea Pigs; Histamine H1 Antagonists; In Vitro Techniques; Isoproterenol; Ovalbumin; Pulmonary Circulation; Respiration; Serotonin Antagonists

Topics: Anaphylaxis; Animals; Bile Acids and Salts; Bradykinin; Carboxy-Lyases; Esophagus; Guinea Pigs; Histamine; Histamine H1 Antagonists; Hypersensitivity; In Vitro Techniques; Muscle Contraction; Ovalbumin; Quinolines; Serotonin

Topics: Anaphylaxis; Animals; Antigen-Antibody Reactions; Egg White; Escherichia coli; Female; Food Hypersensitivity; Lipopolysaccharides; Ovalbumin; Pertussis Vaccine; Polysaccharides, Bacterial; Propranolol; Rats; Zymosan

Topics: Anaphylaxis; Animals; Antigens; Blood Pressure; Cats; Ear, Inner; Electronics, Medical; Guinea Pigs; Haplorhini; Intracranial Pressure; Labyrinthine Fluids; Manometry; Methods; Osmotic Pressure; Ovalbumin; Pressure

Topics: Aerosols; Anaphylaxis; Animals; Antigen-Antibody Reactions; Antigens; Desensitization, Immunologic; Egg White; Guinea Pigs; Immune Sera; Injections, Intravenous; Ovalbumin; Swine; Time Factors

Topics: Aerosols; Anaphylaxis; Animals; Desensitization, Immunologic; Guinea Pigs; Injections, Intraperitoneal; Ovalbumin; Seizures; Time Factors

Topics: Aerosols; Anaphylaxis; Animals; Antigens; Female; Guinea Pigs; Injections, Intravenous; Ovalbumin; Time Factors

Topics: Agglutination; Anaphylaxis; Animals; Antigen-Antibody Reactions; Blood Circulation; Blood Pressure; Blood Transfusion; Catheterization; Drug Hypersensitivity; Heparin; Hypotension; Leukocytes; Ovalbumin; Perfusion; Rats; Vasodilator Agents

Topics: Anaphylaxis; Animals; Antigen-Antibody Reactions; Blood Glucose; Bradykinin; Dextrans; Hot Temperature; Injections, Intravenous; Insulin; Male; Ovalbumin; Polysaccharides; Rats; Wounds and Injuries

Topics: Anaphylaxis; Animals; Bradykinin; Breeding; Dextrans; Female; Genes, Recessive; Genetics, Population; Heterozygote; Male; Ovalbumin; Rats; Serotonin

The antigen-induced release of SRS-A and histamine was studied in the guinea pig and rat using whole and fractionated antiserum preparations. Guinea pig 7Sgamma(1)-antibody sensitized sliced guinea pig lung tissue for antigen-induced release of both SRS-A and histamine; neither substance was released from lung tissue prepared with 7Sgamma(1)-antibody. Rats injected intraperitoneally with hyperimmune rabbit or rat antiserum released only SRS-A in significant amounts when challenged with antigen by the same route. A definite time interval between the injection of antiserum and challenge with antigen was required for optimal release of SRS-A. Fractionation of rat antiserum demonstrated that the immunoglobulin responsible for most of the SRS-A release from rat peritoneal tissue was a gammaG-antibody or fraction thereof. Acting in this capacity, the gammaG-antibody or its subfraction may be considered a second type of homocytotropic antibody. Fractions of rat antisera containing the first type of homocytotropic antibody, i.e. antibody mediating release of histamine and serotonin, prepared peritoneal tissues for the release of large amounts of these pharmacological agents and only small amounts of SRS-A. Two different mechanisms for the production of PCA lesions in the rat were considered. One of these involves the antigen-induced release of histamine and serotonin from mast cells sensitized by homocytotropic antibody. This reaction has an optimal latent period of 24-72 hr. The second mechanism involves the local combination of antigen with "hyperimmune" heterologous or homologous antisera. This reaction can be elicited after a latent period of 4 but not 24 hr; host complement and leukocyte lysosomal enzymes, as well as SRS-A, may be involved.

Topics: Anaphylaxis; Animals; Antibodies; Antigen-Antibody Reactions; Chromatography; Fibrinogen; gamma-Globulins; Guinea Pigs; Histamine Release; Immunoelectrophoresis; Lung; Ovalbumin; Rats; Serum Albumin, Bovine; SRS-A

Topics: Amine Oxidase (Copper-Containing); Anaphylaxis; Animals; Guinea Pigs; Histamine; Histamine Release; Male; Ovalbumin; Serum Albumin, Bovine

Topics: Amine Oxidase (Copper-Containing); Anaphylaxis; Animals; Antibodies; Guinea Pigs; Heart; Histamine Release; In Vitro Techniques; Kinetics; Male; Ovalbumin; Semicarbazides; Temperature

Topics: Anaphylaxis; Animals; Antigens; Biological Assay; Female; Guinea Pigs; Histamine; Histamine Release; Hypersensitivity; Ileum; Immune Sera; Liver; Lung; Male; Muscle Contraction; Ovalbumin; Rabbits; Stimulation, Chemical; Time Factors

Topics: Anaphylaxis; Animals; Antigens; Chickens; Histamine Release; Ovalbumin; Rats

Topics: Amine Oxidase (Copper-Containing); Anaphylaxis; Animals; Guinea Pigs; Heparin; Ovalbumin; Protamines

Topics: Amine Oxidase (Copper-Containing); Anaphylaxis; Animals; Carotid Arteries; Guanidines; Guinea Pigs; Heparin; Histamine; Jugular Veins; Ovalbumin; Shock, Septic; Toxins, Biological

Topics: Anaphylaxis; Animals; Antigen-Antibody Reactions; Arthus Reaction; Coloring Agents; Guinea Pigs; Injections, Intravenous; Male; Ovalbumin; Skin Tests

Topics: Adrenal Glands; Anaphylaxis; Animals; Autacoids; Blood Pressure; Bradykinin; Epinephrine; Female; Guinea Pigs; Histamine; Male; Muscle, Smooth; Ovalbumin; Poultry; Rats; Rectum; Regional Blood Flow; Stomach

Topics: Acetylcholine; Adrenalectomy; Anaphylaxis; Animals; Aspirin; Atropine; Bradykinin; Catecholamines; Ethanolamines; Guinea Pigs; Hexamethonium Compounds; Histamine; Histamine H1 Antagonists; Kinins; Kymography; Lung; Methysergide; ortho-Aminobenzoates; Ovalbumin; Serotonin; SRS-A; Sympathectomy; Tolazoline

Topics: Anaphylaxis; Animals; Guinea Pigs; Heart; Heart Failure; Histamine H1 Antagonists; Lung; Ovalbumin; Papaverine; Toxins, Biological

Topics: Amine Oxidase (Copper-Containing); Anaphylaxis; Animals; Guinea Pigs; Liver; Ovalbumin; Prednisolone

Topics: Amine Oxidase (Copper-Containing); Anaphylaxis; Animals; Female; Guinea Pigs; Heparin; Liver; Male; Ovalbumin

Topics: Anaphylaxis; Animals; Asthma; Blood Pressure; Electrocardiography; Electromyography; Guinea Pigs; Heart Rate; Lung; Ovalbumin; Plethysmography; Pulmonary Circulation; Respiration

Topics: Anaphylaxis; Animals; Antigen-Antibody Reactions; Antigens; Binding Sites; Chromatography, Gel; Chromium Isotopes; Guinea Pigs; In Vitro Techniques; Iodine Isotopes; Kidney; Liver; Lung; Myocardium; Ovalbumin; Rabbits

Topics: Anaphylaxis; Anesthesia; Animals; Antibodies; Antigens; Blood-Brain Barrier; Electroencephalography; Ovalbumin; Pentobarbital; Rabbits; Sodium

Topics: Anaphylaxis; Animals; Antigen-Antibody Reactions; Histamine Release; In Vitro Techniques; Mast Cells; Mice; Ovalbumin; Peritoneal Cavity

Topics: Anaphylaxis; Animals; Antigen-Antibody Reactions; Cortisone; Female; Guinea Pigs; Histamine Release; Ileum; In Vitro Techniques; Kymography; Male; Ovalbumin

Topics: Anaphylaxis; Animals; Desensitization, Immunologic; Esterases; Guinea Pigs; Histamine Release; Lung; Ovalbumin; Serum Albumin, Bovine

Topics: Anaphylaxis; Animals; Antigens; Blood Pressure; Blood-Brain Barrier; Carotid Arteries; Electrocardiography; Electroencephalography; Guinea Pigs; Injections, Intraperitoneal; Injections, Intravenous; Ovalbumin; Rabbits; Trypan Blue

Topics: Anaphylaxis; Animals; Antibodies; Chromatography, Gel; Dextrans; gamma-Globulins; Immune Sera; Immunoelectrophoresis; Ovalbumin; Precipitins; Rabbits

Topics: Anaphylaxis; Animals; Antigen-Antibody Reactions; Histamine Release; In Vitro Techniques; Mast Cells; Mice; Ovalbumin; Peritoneum; Serotonin

Topics: Anaphylaxis; Animals; Blood Platelets; Fibrinolysis; Heparin; Ovalbumin; Rats

Topics: Anabolic Agents; Anaphylaxis; Animals; Antibody Formation; Guinea Pigs; Hemagglutination; Hyaluronoglucosaminidase; Mice; Ovalbumin; Passive Cutaneous Anaphylaxis; Prednisolone; Rabbits

Topics: Adolescent; Adult; Anaphylaxis; Animals; Asthma; Dexamethasone; Dogs; Female; Humans; Lung; Male; Ovalbumin; Rabbits; Serotonin

Muscle strips taken from chronically denervated hemidiaphragms of guinea pigs immunized to ovalbumin react in vitro to the administration of small amounts of this protein with a contraction similar to that of visceral muscle in the Schultz-Dale reaction. A sustained shortening is produced by histamine on denervated diaphragmatic muscle from both sensitized and nonsensitized guinea pigs.

Topics: Abdominal Muscles; Acetylcholine; Anaphylaxis; Animals; Denervation; Diaphragm; Guinea Pigs; Histamine; Immunization; Muscle Denervation; Muscle, Skeletal; Muscles; Ovalbumin; Pharmacology; Research; Serum Albumin

Rats and guinea pigs were depleted of complement (C') by treatment with heat aggregated human gamma-globulin (agg HGG), zymosan, anti-beta1C globulin, and carrageenan. Although antigen and antibody were bound to vascular structures, Arthus reactions were inhibited. This inhibition was characterized by the lack of C' binding to walls of vessels, the lack of polymorphonuclear (PMN's) cellular infiltrates, and the lack of significant vascular damage. When the same animals were followed for several hours thereafter, levels of serum C' began to rise, C' was bound in tissues, PMN infiltrates appeared, and immunologic vasculitis developed. Blood counts, chemotaxis of PMN's induced by lysates of PMN granules, together with studies on motility and phagocytosis by PMN's obtained from C' depleted rats, failed to establish any abnormality in these cells which would account for inhibition of Arthus reactions. The specificity of C' depletion in terms of effects in the first four reacting components of guinea pig C' was studied. Treatment with agg HGG led to loss of activity in all components, whereas zymosan and anti-beta1C globulin predominately affected the third component (C'3c). Carrageenan mainly affected the first two reacting components of C'. Thus, the availability of the 3c component, or a subsequently reacting component, correlated with the attraction of PMN's to immune reactants in vivo. Various antibodies with different C' fixing capacities in vitro were tested for their ability to induce immunologic vasculitis in normal animals. In rats, only those antibodies which fixed C' in vitro possessed biological activity, whereas in guinea pigs, all antibodies tested, regardless of C' fixation in vitro, induced Arthus reactions. For a given antibody in rats the vasculitis-inducing property was reflected in its ability to bind C' in vascular structures. Rats depleted of circulating PMN's by specific antibody were tested for Arthus activity. Although concentrations of immune reactants and C' were readily detected in vascular structures, no PMN infiltration occurred and significant vascular damage was averted.

Topics: Anaphylaxis; Animals; Antibodies; Arthus Reaction; Carrageenan; Chemotaxis; Chromatography; Complement System Proteins; gamma-Globulins; Guinea Pigs; Immunoelectrophoresis; Neutrophils; Ovalbumin; Pathology; Phagocytosis; Polysaccharides; Rats; Research; Vascular Diseases; Zymosan

Topics: Albumins; Anaphylaxis; Animals; Antigens; Guinea Pigs; Ileum; In Vitro Techniques; Muscle, Smooth; Muscles; Ovalbumin; Research; Serum Albumin

Lewis rats, thymectomized at 5 weeks of age and irradiated at 8 weeks, received grafts of adult thymus and marrow, one or both grafts being derived from donors tolerant to bovine gamma-globulin. Challenge 3 or 6 weeks after grafting showed that delayed sensitization could not be induced in animals which received a tolerant thymus or tolerant thymus and marrow, though sensitization to a heterologous antigen (chicken ovalbumin) occurred normally. Arthus reactivity was regained slowly in animals receiving normal thymus and marrow and, to an equal extent, in those receiving grafts from tolerant donors.

Topics: Anaphylaxis; Animals; Antibody Formation; Arthus Reaction; Bone Marrow; Bone Marrow Transplantation; Immune Tolerance; Ovalbumin; Radiation Effects; Rats; Rats, Inbred Lew; Research; Skin Tests; Thymectomy; Thymus Gland; Transplantation Immunology; Transplantation, Homologous

Topics: Adrenal Insufficiency; Adrenalectomy; Adrenocortical Hyperfunction; Anaphylaxis; Antigens; Haemophilus; Ovalbumin; Periodicity; Research; Vaccines

Topics: Anaphylaxis; Animals; Blood; Blood Pressure; Bradykinin; Dogs; Enzyme Precursors; Guinea Pigs; Histamine H1 Antagonists; Ovalbumin; Rabbits

Topics: Anaphylaxis; Animals; Antigens; Female; gamma-Globulins; Guinea Pigs; Histamine Release; Ileum; Lung; Muscle Contraction; Muscle, Smooth; Ovalbumin; Uterus

Topics: Anaphylaxis; Animals; Antigens; Female; gamma-Globulins; Guinea Pigs; Histamine Release; Ileum; Lung; Muscle Contraction; Muscle, Smooth; Ovalbumin; Serum Albumin; Uterus

Topics: Anaphylaxis; Animals; Brain; Guinea Pigs; In Vitro Techniques; Lipid Metabolism; Liver; Lung; Ovalbumin

Topics: Anaphylaxis; Animals; Body Temperature Regulation; Guinea Pigs; Injections, Intraperitoneal; Injections, Intravenous; Movement Disorders; Ovalbumin; Seizures; Shivering

Topics: Anaphylaxis; Animals; Anterior Chamber; Capillary Permeability; Guinea Pigs; Leukocytosis; Ovalbumin; Uvea; Vitreous Body

Topics: Anaphylaxis; Animals; Fluoresceins; Guinea Pigs; Heart; In Vitro Techniques; Ovalbumin

Topics: Anaphylaxis; Animals; Blood Chemical Analysis; Catecholamines; Chlorprothixene; Epinephrine; Lagomorpha; Muramidase; Nialamide; Norepinephrine; Ovalbumin; Prednisone; Rabbits; Research; Serotonin; Shock

Topics: Anaphylaxis; Edema; Electrons; Guinea Pigs; Hypersensitivity, Delayed; Macrophages; Microscopy; Microscopy, Electron; Ovalbumin; Research; Skin; Toxicology

Topics: Anaphylaxis; Animals; Guinea Pigs; Heart; Histamine; Histamine Release; Isoproterenol; Myocardium; Norepinephrine; Ovalbumin; Pharmacology; Rats; Research; Reserpine; Sympatholytics; Sympathomimetics

Topics: Anaphylaxis; Animals; Antigen-Antibody Reactions; Antigens; Biomedical Research; Drug Hypersensitivity; Guinea Pigs; Hemagglutination; Ovalbumin; Penicillin G; Penicillins; Rabbits; Research; Serum Albumin; Skin Tests; Toxicology

Topics: Anaphylaxis; Animals; Body Fluids; Body Weight; Ovalbumin; Rabbits; Research

Topics: Anaphylaxis; Animals; Capillaries; Diphenhydramine; Electrons; Ferritins; Guinea Pigs; Hypersensitivity; Immune System Phenomena; Lung; Microscopy; Microscopy, Electron; Ovalbumin; Pharmacology; Research; Thrombosis

Topics: Anaphylaxis; Animals; gamma-Globulins; Guinea Pigs; Hypersensitivity, Delayed; Ovalbumin; Research; Skin Tests; Transplantation Immunology

Topics: Acetylcholine; Anaphylaxis; Animals; Barium; Caffeine; Epinephrine; Guinea Pigs; Heart Atria; Histamine; Myocardium; Ovalbumin; Pharmacology; Potassium; Research; Serotonin

Topics: Anaphylaxis; Animals; Antigens; Cattle; Encephalomyelitis; Freund's Adjuvant; Guinea Pigs; Lymph Nodes; Ovalbumin; Rats; Research; Serum Albumin; Serum Albumin, Bovine; Spinal Cord; Thymus Gland; Tuberculin Test

Topics: Anaphylaxis; Animals; Guinea Pigs; Histamine Release; In Vitro Techniques; Lung; Mast Cells; Ovalbumin; Peritoneal Cavity; Rats; Research; Toxicology

Topics: Anaphylaxis; Animals; Diabetes Mellitus, Experimental; Dietary Carbohydrates; Glucose; Granulation Tissue; Granuloma; Insulin; Mice; Ovalbumin; Pharmacology; Research

Topics: Anaphylaxis; Animals; Electroencephalography; Guinea Pigs; Histamine; Immune Sera; Injections; Injections, Intraperitoneal; Ovalbumin; Rabbits; Research

Topics: Anaphylaxis; Dextrans; Genetics; Hypersensitivity; Immune System Diseases; Ovalbumin; Rats; Research; Toxicology

Topics: Anaphylaxis; Dextrans; Egg White; Hypersensitivity; Inflammation; Ovalbumin; Pharmacology; Rats; Research; Toxicology; Trypsin Inhibitors; Vascular Diseases

Topics: Anaphylaxis; Animals; Antibody Formation; Immunization; In Vitro Techniques; Ovalbumin; Research; Research Design; Swine; Tissue Culture Techniques; Vaccination

Topics: Anaphylaxis; Animals; Freund's Adjuvant; Guinea Pigs; Ovalbumin; Plasma Cells; Research; Tuberculin Test

Topics: Adjuvants, Immunologic; Adjuvants, Pharmaceutic; Aminocaproates; Aminocaproic Acid; Anaphylaxis; Epinephrine; Norepinephrine; Ovalbumin; Pharmacology; Physiology; Rats; Research; Vasomotor System

Topics: Anaphylaxis; Antibodies; Antigens; gamma-Globulins; Immune System Phenomena; In Vitro Techniques; Ovalbumin

Topics: Anaphylaxis; Animals; Anti-Allergic Agents; Asthma; Guinea Pigs; Histamine H1 Antagonists; Histamine Release; Ileum; Muscle, Smooth; Ovalbumin; Platinum; Research; Salts; Toxicology

Topics: Anaphylaxis; Animals; Antigen-Antibody Reactions; Antigens; Cattle; Dogs; Freund's Adjuvant; Hemagglutination; Hemagglutination Tests; Ovalbumin; Precipitin Tests; Serum Albumin; Serum Albumin, Bovine

A short term model in which circulating antigen-antibody complexes and host complement localized in vessel walls of guinea pigs was analyzed. Localization was accomplished by subjecting the animals to anaphylactic shock. The circulating macromolecules, such as antigen-antibody complexes, appeared to localize by being trapped in the vessel wall along the basement membrane that acted as a filter during a state of increased permeability of the vessel. It was suggested that this point of localization between the endothelial cell and the basement membrane may well represent the earliest focus of inflammation in diseases caused by the deposition of injurious macromolecules such as soluble antigen-antibody complexes from the blood stream. Complexes localized in the vessel walls did not provoke Arthus-type vasculonecrotic reactions even though in both these vessels and in cutaneous Arthus reactions antibody, antigen, and host complement (C'3c) were deposited in the vessel walls. The possibility was presented that since circulating macromolecules and probably complexes deposited in (a) relatively small amounts, and (b) in a position beneath endothelial cells, they were not strongly chemotactic toward circulating polymorphonuclear leukocytes. Vasculonecrotic reactions, therefore, were not observed. It was brought out that this may be similar to the situation in glomerulonephritis induced by localized immune complexes, in which severe necrosis is not observed. In the Arthus vascular reaction, host complement was found microscopically accumulated with the immune reactants in affected vessel walls.

Topics: Anaphylaxis; Animals; Antibodies; Antigen-Antibody Complex; Antigen-Antibody Reactions; Arthus Reaction; Blood Vessels; Cattle; Complement System Proteins; Electrons; Fluorescent Antibody Technique; gamma-Globulins; Glomerulonephritis; Guinea Pigs; Immune Sera; Immunoelectrophoresis; Inflammation; Microscopy; Microscopy, Electron; Necrosis; Neutrophils; Ovalbumin; Pathology; Rabbits; Research; Serum Albumin; Serum Albumin, Bovine; Vascular Diseases

Topics: Anaphylaxis; Animals; Antigen-Antibody Reactions; Antigens; Dinitrophenols; Freund's Adjuvant; Guinea Pigs; Haptens; Injections; Lysine; Naphthalenes; Ovalbumin; Penicillin G; Peptides; Pharmacology; Research; Toluene

Topics: Anaphylaxis; Animals; Anti-Allergic Agents; Bradykinin; Guinea Pigs; Histamine H1 Antagonists; Intestines; Muramidase; Muscle, Smooth; Ovalbumin; Pharmacology; Piperidines; Prednisone; Rabbits; Research; Selective Serotonin Reuptake Inhibitors; Serotonin; Thioxanthenes; Xanthenes

Topics: Anaphylaxis; Anesthetics, Local; Animals; Antigens; Blood Volume Determination; Cocaine; Coronary Vessels; Dibucaine; Guinea Pigs; Heart; Lidocaine; Ovalbumin; Procaine; Research

Topics: Anaphylaxis; gamma-Globulins; Ovalbumin

The quantitative release of histamine by specific antigen from perfused, chopped, sensitized guinea pig lung has been used to study the effect of peptidase substrates and inhibitors on the anaphylactic reaction. The anaphylactic release of histamine is prevented by chymotrypsin substrates and inhibitors but not by trypsin, carboxypeptidase, or leucine aminopeptidase substrates or the soybean trypsin inhibitor. The chymotrypsin substrates and inhibitors appear to be acting on an antigen-antibody-activated step because these substances fail to inhibit if the tissue is washed free of them prior to antigen addition, and because there is complete desensitization of the tissue without histamine release when the antigen is added in the presence of these inhibitors. The inhibitors work equally well in tissue from passively sensitized animals or in tissue from animals actively sensitized with either ovalbumin or bovine gamma globulin. These observations suggest that activation of a chymotrypsin-like enzyme is a necessary condition for the anaphylactic release of histamine in guinea pig lung. Diisopropylfluophosphate is inhibitory when present at the time of antigen addition but not when the tissue is washed free of unfixed diisopropylfluophosphate prior to adding antigen. This indicates that diisopropylfluophosphate must be acting exclusively on an enzyme which exists in lung tissue in a precursor form resistant to diisopropylfluophosphate until activated by the antigen-antibody interaction. Thiol alkylating or oxidizing agents also prevent the anaphylactic release of histamine, but in contrast to the situation with diisopropylfluophosphate and the other chymotrypsin inhibitors, the phase of the anaphylactic reaction inhibited by N-ethylmaleimide is available prior to the antigen-antibody interaction. The similarities and differences between immune hemolysis and anaphylaxis in chopped guinea pig lung are considered in detail.

Topics: Amino Acids; Anaphylaxis; Animals; Antigens; Guinea Pigs; Histamine; Histamine Release; Hypersensitivity; Lung; Ovalbumin; Peptide Hydrolases; Peptides; Protease Inhibitors

Topics: Anaphylaxis; Egg White; Formaldehyde; Guinea Pigs; Hot Temperature; Ovalbumin; Ovum

Sera of fourteen rabbits injected with alum-precipitated recrystallized ovaltumin, containing 0.046 to 0.604 mg. of precipitable antibody nitrogen per ml. (average 0.299 mg.), passively sensitized human skin, while the sera of nine rabbits injected with dissolved recrystallized ovalbumin, containing from less than 0.05 to 0.420 of antibody nitrogen per ml. (average 0.176 mg. or less), were inactive in human skin. The skin-sensitizing activity of the sera bore no relation to the precipitin content. Removal of 68 to 90 per cent of the precipitin nitrogen by a single addition of antigen did not affect the activity of the sera in sensitizing human skin. Removal of all precipitable antibody nitrogen in one serum by a single addition of antigen removed the skin-sensitizing activity. The "univalent" antibody remaining after complete removal of precipitin by fractional addition of antigen showed the same activity in passive sensitization of human skin as the original serum.

Topics: Anaphylaxis; Animals; Antibodies; Antigens; Humans; Hypersensitivity; Immunization, Passive; Ovalbumin; Rabbits; Skin