calcimycin and Anaphylaxis

Tripterine (TRI), an active monomer in Tripterygium wilfordii, has significant pharmacological activities, such as anti-inflammatory, immunosuppressive and anti-tumor activities. TRI may be used to treat allergic diseases because of its characteristics of immunosuppression.. This study aims to explore the anti-allergic effect of TRI.. It was tested in vivo and in vitro in this study.. The results showed that TRI could significantly inhibit histamine release from rat peritoneal mast cells; the inhibitory effect of TRI on histamine release was stronger than that of other known histamine inhibitors such as disodium cromoglyceride. TRI also significantly inhibited systemic anaphylactic shock induced by compound 48/80 and skin allergy induced by IgE, and inhibited the expression of inflammatory factors secreted by Human Mast Cells (HMC-1) induced by Phorbol 12-Myristate 13- Acetate (PMA) and calcium carrier A23187. In the animal model of allergic rhinitis induced by Ovalbumin (OA), the scores of friction, histamine, IgE, inflammatory factors and inflammatory cells decreased after TRI was administered orally or nasally.. TRI, as an active immunoregulatory factor, has great potential in the treatment of mast cell-mediated allergic diseases.

Topics: Anaphylaxis; Animals; Anti-Allergic Agents; Calcimycin; Cytokines; Disease Models, Animal; Drugs, Chinese Herbal; Histamine Release; Humans; Male; Mast Cells; Mice, Inbred BALB C; NF-kappa B; p-Methoxy-N-methylphenethylamine; Pentacyclic Triterpenes; Rats; Rhinitis, Allergic; Tetradecanoylphorbol Acetate; Triterpenes

Oleanolic acid (OA) is an active compound found in a variety of medicinal herbs and plants. Though OA has been widely attributed with a variety of biological activities, studies focused on its anti-allergic inflammation properties are insufficient.. Given the rapid increase in allergic diseases and the lack of fundamental treatment options, this study aimed to find a safe and effective therapy for allergic disorders.. We evaluated the inhibitory effect of OA on allergic inflammatory response and the possible mechanisms underlying the effect using phorbol-12-myristate 13-acetate plus calcium ionophore A23187 (PMACI)-stimulated human mast cell (HMC)-1, and a mouse model of compound 48/80-induced anaphylactic shock.. OA suppressed pro-inflammatory cytokine expressions in PMACI-induced HMC-1 cells by inhibiting activation of the Akt, p38 mitogen-activated protein kinase (MAPK), nuclear factor-κB (NF-κB), and signal transducer and activator of transcription (STAT) 1 signaling pathways. Moreover, OA showed a protective effect against compound 48/80-induced anaphylactic shock through inhibition of histamine release and immunoglobulin E level via regulation of NF-κB and STAT1 activation.. The results showed that OA suppressed mast cell-mediated allergic response by transcriptional regulation. We suggest that OA has potential effect against allergic inflammatory disorders, including anaphylaxis, and might be a useful therapeutic agent for allergic disease.

Topics: Anaphylaxis; Animals; Anti-Allergic Agents; Calcimycin; Cell Line; Cytokines; Histamine Release; Humans; Inflammation; Inflammation Mediators; Male; Mast Cells; Mice, Inbred ICR; NF-kappa B; Oleanolic Acid; p-Methoxy-N-methylphenethylamine; p38 Mitogen-Activated Protein Kinases; Phorbol Esters; Proto-Oncogene Proteins c-akt; STAT1 Transcription Factor

Xanthone is a phenolic compound found in a few higher plant families; it has a variety of biological activities, including antioxidant, anti-inflammatory, and anticancer properties. However, the molecular and cellular mechanisms underlying the activity of xanthone in allergic contact dermatitis (ACD) remain to be explored. Therefore, this study aimed to investigate the regulatory effects of xanthone in ACD in human keratinocytes (HaCaT cell), and human mast cell line (HMC-1 cell) in vitro and in an experimental murine model. The results demonstrated that treatment with xanthone reduced the production of pro-inflammatory cytokines and chemokines including interleukin (IL)-1β, IL-6, IL-8, and expression of chemokines thymus and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC) in tumor necrosis factor (TNF)-α and interferon (IFN)-γ-stimulated HaCaT cells. Xanthone also suppressed the production of pro-inflammatory cytokines, chemokines, and allergic mediators in phorbol myristate acetate/A23187 calcium ionophore (PMACI)-stimulated HMC-1 cells. Xanthone significantly suppressed the phosphorylation of mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB) and activation of caspase-1 signaling pathway in vitro model. Additionally, xanthone administration alleviated 2,4-dinitrofluorobenzene (DNFB)-induced atopic dermatitis like-skin lesion by reducing the serum levels of immunoglobulin E (IgE), histamine, and pro-inflammatory cytokines and suppressing MAPKs phosphorylation. Xanthone administration also inhibited mortality due to compound 48/80-induced anaphylactic shock and suppressed the passive cutaneous anaphylaxis (PCA) reaction mediated by IgE. Collectively, these results suggest that xanthone has a potential for use in the treatment of allergic inflammatory diseases.

Topics: Administration, Oral; Anaphylaxis; Animals; Anti-Allergic Agents; Calcimycin; Cell Line; Dermatitis, Allergic Contact; Dinitrofluorobenzene; Disease Models, Animal; Drug Evaluation, Preclinical; Humans; Inflammation Mediators; Keratinocytes; Male; Mast Cells; Mice; Mitogen-Activated Protein Kinases; p-Methoxy-N-methylphenethylamine; Phosphorylation; Skin; Tetradecanoylphorbol Acetate; Xanthones

The antiallergic effects of traditional medicines have long been studied. Traditional Korean medicine, Citrus sunki and bamboo salt, has been used for the treatment of allergic diseases in Korea. K-ALL, composed of Citrus sunki and bamboo salt, is a newly prepared prescription for allergic patients. To develop the new antiallergic agent, we examined the effects of K-ALL through in vivo and in vitro models. K-ALL and naringin (an active compound of K-ALL) significantly inhibited histamine release from rat peritoneal mast cells. This inhibitory effect of K-ALL on histamine release was higher than effects from other known histamine inhibitors such as bamboo salt, Citrus sunki or disodium cromoglycate. K-ALL significantly inhibited systemic anaphylactic shock induced by the compound 48/80 and passive cutaneous anaphylaxis induced by the IgE. K-ALL also inhibited production and mRNA expression of inflammatory cytokines induced by phorbol 12-myristate 13-acetate and the calcium ionophore A23187 on HMC-1 cells (a human mast cell line). In the ovalbumin-induced allergic rhinitis animal model, rub scores, histamine, IgE, inflammatory cytokines and inflammatory cell counts were all reduced by the oral or nasal administration of K-ALL (pre and posttreatment). These results indicate the great potential of K-ALL as an active immune modulator for the treatment of mast cell-mediated allergic diseases.

Topics: Administration, Intranasal; Administration, Oral; Anaphylaxis; Animals; Calcimycin; Calcium Ionophores; Carcinogens; Cell Line; Citrus; Cytokines; Disease Models, Animal; Gene Expression Regulation; Humans; Inflammation Mediators; Male; Mast Cells; Medicine, Korean Traditional; Mice; Mice, Inbred ICR; Plant Extracts; Rats; Rats, Sprague-Dawley; Rhinitis, Allergic; Rhinitis, Allergic, Perennial; Tetradecanoylphorbol Acetate

Chitin is the polysaccharide and is found in insects, parasites and fungi. Chitin has shown various immunological effects in in vivo and in vitro models. In this study, crystallinity controlled N-acetyl glucosamine (CCG) which has a high solubility was prepared from the low molecular weight chitosan. However, the effect of CCG in an allergic response is not clear.. To investigate the effect and regulatory mechanism of CCG on allergic responses.. To demonstrate the effect of CCG, we induced systemic anaphylactic shock, ear swelling response, passive cutaneous anaphylaxis (PCA), and inflammatory reaction.. CCG inhibited the compound 48/80-induced systemic anaphylactic shock and ear swelling responses. IgE-mediated PCA was inhibited by the oral administration or topical application of CCG. Histamine and β-hexosaminidase release from mast cells was decreased with the treatment of CCG. CCG also inhibited phorbol 12-myristate 13-acetate and calcium ionophore A23187-induced interleukin-1β production and mRNA expression by suppressing NF-κB activation and IκBα phosphorylation. Furthermore, CCG suppressed the activation of caspase-1.. These results suggest that CCG may have beneficial applicability as a candidate for an anti-allergic agent.

Topics: Acetylglucosamine; Anaphylaxis; Animals; Anti-Allergic Agents; Calcimycin; Calcium Ionophores; Carcinogens; Caspase 1; Cell Line; Enzyme Activation; Gene Expression Regulation; Hexosaminidases; Histamine; Humans; Interleukin-1beta; Male; Mast Cells; Mice; Mice, Inbred ICR; Rats; Rats, Sprague-Dawley; RNA, Messenger; Tetradecanoylphorbol Acetate

Insamhodo-tang (IHT) has traditionally been used in Korea to treat a variety of diseases, including chronic cough, tuberculosis, and chronic bronchitis. However, the anti-allergic and anti-inflammatory effects of IHT and its molecular mechanisms have yet to be clearly elucidated. In this study, we attempted to evaluate the effects of IHT on mast cell-mediated allergy inflammation in vitro and in vivo.. We investigated to ascertain the pharmacological effects of IHT on both compound 48/80-induced and 2,4-dinitrofluorobenzene (DNFB)-induced allergic reactions under in vivo conditions. Additionally, to find a possible explanation for the anti-inflammatory mechanisms of IHT, we evaluated the regulatory effects of IHT on the level of inflammatory mediators in phorbol 12-myristate 13-acetate plus calcium ionophore A23187 (PMACI)-stimulated human mast cells (HMC-1).. The finding of this study demonstrated that IHT reduced compound 48/80-induced systemic anaphylactic shock, DNFB-induced dermatitis, and ear swelling responses in mice. Additionally, IHT inhibited the production of interleukin (IL)-6, IL-8, and TNF-α, as well as the activation of nuclear factor-κB and caspase-1 in PMACI-stimulated HMC-1.. Collectively, the findings of this study provide us with a novel insight into the pharmacological actions of IHT as a potential molecule for use in the treatment of allergic inflammation diseases.

Topics: Anaphylaxis; Animals; Anti-Inflammatory Agents; Calcimycin; Dermatitis; Dinitrofluorobenzene; Edema; Humans; Hypersensitivity; Inflammation; Inflammation Mediators; Ionophores; Male; Mast Cells; Medicine, Korean Traditional; Mice; Mice, Inbred BALB C; Mice, Inbred ICR; p-Methoxy-N-methylphenethylamine; Phytotherapy; Plant Extracts

Leaves of Eriobotrya japonica Lindl. (Rosaceae) (LEJL) have been used as traditional medicines for inflammatory diseases and chronic bronchitis. However, its effect on mast cell-mediated anaphylactic reaction is not known. The anaphylactic allergic reaction is involved in many allergic diseases such as asthma and allergic rhinitis. In this report, we investigate the effect of LEJL on the anaphylactic allergic reaction and studied its possible mechanisms of action. LEJL inhibited compound 48/80-induced systemic anaphylactic reactions and serum histamine release in mice. LEJL dose-dependently decreased the IgE-mediated passive cutaneous anaphylaxis and histamine release from mast cells. Furthermore, LEJL decreased the production of tumor necrosis factor-alpha in phorbol 12-myristate 13-acetate and A23187-stimulated human mast cells. These findings provide evidence that LEJL could be a candidate as an anti-allergic agent.

Topics: Anaphylaxis; Animals; Anti-Allergic Agents; Calcimycin; Eriobotrya; Histamine; Histamine Release; Humans; Immunoglobulin E; Male; Mast Cells; Mice; Mice, Inbred ICR; p-Methoxy-N-methylphenethylamine; Plant Leaves; Rats; Rats, Sprague-Dawley; Tetradecanoylphorbol Acetate; Tumor Necrosis Factor-alpha

The discovery of drugs for the treatment of allergic disease is an important subject in human health. Stimulation of mast cells starts the process of degranulation resulting in releasing of mediators, such as histamine. In this report, we investigated the effect of aqueous extract of Dracocephalum argunense Fisch. (Labiatae) (DAAE) on the mast cell-mediated allergic response and studied its possible mechanisms of action, focusing on the histamine release and pro-inflammatory cytokine secretion in mast cells. DAAE inhibited compound 48/80-induced systemic reactions and serum histamine release in mice. In addition, DAAE attenuated IgE-mediated skin allergic reaction. DAAE dose-dependently reduced IgE-induced histamine release from mast cells. The level of cAMP was transiently increased by treatment of DAAE. DAAE specifically blocked the phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187-induced p38 mitogen-activated protein kinase (MAPK) activation. DAAE decreased the secretion of pro-inflammatory cytokines, such as tumor necrosis factor-alpha and interleukin-6 in mast cells. Our findings provide evidence that DAAE inhibits mast cell derived allergic reactions, and involvement of cAMP for histamine release and p38 MAPK for pro-inflammatory cytokine secretion in these effects.

Topics: Anaphylaxis; Animals; Anti-Allergic Agents; Blotting, Western; Calcimycin; Cyclic AMP; Histamine Release; Hypersensitivity; Immunoglobulin E; Interleukin-6; Lamiaceae; Male; Mast Cells; Mice; Mice, Inbred ICR; p-Methoxy-N-methylphenethylamine; p38 Mitogen-Activated Protein Kinases; Passive Cutaneous Anaphylaxis; Rats; Rats, Sprague-Dawley; Tetradecanoylphorbol Acetate; Tumor Necrosis Factor-alpha

Heparin binds histamine and has been advocated as a therapy for anaphylactic and anaphylactoid shock. The efficacy of heparin in treating anaphylactoid shock is compared with therapy with diphenhydramine and epinephrine, as well as sham treatment with saline.. This controlled study of 9 anesthetized, intubated pigs induced shock with intravenous calcium ionophore A23187 (5 mg/kg), which is known to degranulate mast cells in vitro. Serum histamine levels were measured using an enzyme-linked immunosorbent assay. Shock, defined as a greater than 20% decrease in mean arterial blood pressure, was treated with intravenous saline, epinephrine with diphenhydramine, or heparin. Data were analyzed using Wilcoxon rank sum and analysis of variance, as appropriate.. All pigs developed anaphylactoid shock after injection with A23187, as evidenced by hypotension, flushing, and an increase in plasma histamine. Mean arterial blood pressure fell from a mean of 73 (SD 10) mm Hg to 28 (SD 16) mm Hg after injection (P<.001; 95% confidence interval [CI] of the difference in pressures 34 to 57 mm Hg). Mean serum histamine levels increased from 712 micromol/dL (SD 731) to 1,154 micromol/dL (SD 799) after injection (Z value -2.201; P=.0277; 95% CI of the difference -610 to -99). Both epinephrine with diphenhydramine and heparin but not saline reversed shock.. A23187 induced anaphylactoid shock in all subjects. Therapy with intravenous epinephrine combined with diphenhydramine reversed shock. Heparin also rapidly reversed shock.

Topics: Adrenergic Agonists; Anaphylaxis; Animals; Calcimycin; Diphenhydramine; Epinephrine; Heparin; Histamine; Histamine H1 Antagonists; Ionophores; Pilot Projects; Prospective Studies; Swine

Bleomycin and asparaginase are widely used antineoplastic agents which may induce allergic or inflammatory side-effects. Mast cells are implicated as effector cells in allergic and inflammatory responses. The aim of this study was to establish whether bleomycin or asparaginase modulate leukotriene production in vitro and in vivo. Leukotriene C4 (LTC4) production by murine bone marrow-derived mast cells (BMMC) was determined by radioimmunoassay (RIA). Leukotriene production in patients was assessed by determining leukotriene E4 and N-acetyl-leukotriene E4 in urine by means of combined HPLC and RIA. Bleomycin induced an up to 2.1-fold increase in LTC4 production both in unstimulated and in calcium ionophore-stimulated mast cells. In 3 of 7 patients treated with bleomycin, a greater than 2-fold increase in endogenous leukotriene production was observed. This effect was associated with febrile responses and was most pronounced in a patient who developed an Adult Respiratory Distress Syndrome (ARDS). Asparaginase increased leukotriene production up to 10-fold in stimulated but not in unstimulated BMMC. In a patient who developed an anaphylactic reaction after treatment with asparaginase, a pronounced increase in urinary leukotriene concentration was observed. In contrast to bleomycin or asparaginase, a number of other cytostatic agents did not significantly change leukotriene production by BMMC. Our data indicate that some of the inflammatory and allergic side-effects of bleomycin and asparaginase could be mediated by leukotrienes, a possible source of which may be mast cells.

Topics: Adult; Anaphylaxis; Animals; Antineoplastic Agents; Asparaginase; Bleomycin; Calcimycin; Drug Hypersensitivity; Humans; In Vitro Techniques; Inflammation; Ionophores; Leukotriene C4; Leukotriene E4; Leukotrienes; Lymphoma, Non-Hodgkin; Mast Cells; Mice; Mice, Inbred BALB C; Respiratory Distress Syndrome

Persistent diarrhea, vomiting, and dehydration are symptoms often seen in patients suffering from food allergy after chronic antigen exposure; however, the precise mechanisms involved have not been well defined. In an effort to clarify the mechanisms of the chronic intestinal changes attributable to genuine IgE-mediated anaphylactic reactions induced by orally administered antigen, a mouse model was established by s.c. implantation of a murine hybridoma capable of producing monoclonal anti-trinitrophenyl IgE antibody, and the morphologic and immunologic changes occurring in the intestine upon chronic antigen exposure were investigated. In the early stage after ingestion of the antigen, diarrhea and noticeable infiltration of mast cells as well as eosinophils into the lamina propria were observed. A substantial increase in serum histamine levels as well as an increase in leukotriene C4 synthesis in the jejunal mucosa were observed 1 h after antigen challenge. Also, the synthesis of leukotriene B4 was significantly elevated for up to 9 h after antigen challenge. The expression of both intercellular adhesion molecule-1 (ICAM-1) on mucosal vascular endothelial cells and IAd on epithelial cells was markedly enhanced, and noticeable infiltration of eosinophils and lymphocytes was also confirmed in the mouse model after chronic antigen exposure. These findings suggest that oral antigen exposure induces anaphylactic reactions in the intestine mediated by mast cells and eosinophils in response to the IgE-antigen complex in the early phase, and also induces lymphocyte migration after chronic antigen exposure.

Topics: Administration, Oral; Anaphylaxis; Animals; Calcimycin; Chemotaxis, Leukocyte; Female; Haptens; Immunoglobulin E; Intercellular Adhesion Molecule-1; Intestinal Mucosa; Ionophores; Leukotriene B4; Leukotriene C4; Mice; Mice, Inbred BALB C; Serum Albumin, Bovine; Trinitrobenzenes

We demonstrate using primary mast cell cultures derived from wild-type and CD45-deficient mice that mast cell triggering through the high-affinity immunoglobulin E (IgE) receptor requires the cell surface tyrosine phosphatase CD45. Unlike wild-type cells, cross-linking of surface-bound IgE in mast cells deficient in CD45 does not induce degranulation. Degranulation in these mutant cells does occur after treatment with the calcium ionophore A23187 indicating that the degranulation machinery is intact in these cells. We also demonstrate that the tyrosine phosphatase inhibitors orthoVanadate and perVanadate inhibit degranulation in wild-type mast cells, as does cross-linking of CD45 by anti-CD45 antibodies. Finally, we show that CD45-deficient mice are resistant to IgE-dependent systemic anaphylaxis. These results show that, like the T cell receptor and the antigen receptor on B cells, there is an absolute requirement for CD45 in signaling via the high affinity IgE receptor, expanding the number of receptors for which CD45 is an essential component.

Topics: Anaphylaxis; Animals; B-Lymphocytes; Calcimycin; Cell Degranulation; Cell Line; Flow Cytometry; Immunoglobulin E; Leukocyte Common Antigens; Mast Cells; Mice; Mice, Inbred C57BL; Mutation; Receptors, Antigen, T-Cell; Vanadates

The effect of ibudilast on anaphylactic bronchoconstriction was studied in guinea pigs sensitized actively with ovalbumin (OA). Animals were treated with indomethacin, tripelennamine and propranolol prior to the antigen challenge. Anaphylactic bronchoconstriction was prevented by ibudilast (1-4 mg/kg i.v. and 5-20 mg/kg p.o.) dose-dependently. FPL55712 and phenidone were also effective. Even when administered at the maximum development of bronchoconstriction, ibudilast (0.5 and 2 mg/kg i.v.) and FPL 55712 caused significant reduction of the increased airway tone, while phenidone did not. Ibudilast (1-4 mg/kg i.v.) and FPL55712 inhibited leukotriene D4-induced airway responses in nonsensitized guinea pigs pretreated with indomethacin and propranolol. Ibudilast (1.6 and 4 mg/kg i.v.) inhibited platelet-activating-factor (PAF)-induced airway responses in nonsensitized guinea pigs pretreated with indomethacin and propranolol, however, FPL 55712 inhibited PAF-induced airway responses only at a high dose such as 10 mg/kg i.v. Ibudilast (4 mg/kg i.v.) did not inhibit acetylcholine-induced airway response. Ibudilast showed inhibition of the release of slow-reacting substance of anaphylaxis (SRS-A) from guinea pig chopped lung sensitized with OA, which was significantly diminished by indomethacin. The drug little affected the activity of phospholipase A2 and 5-lipoxygenase in guinea pig polymorphonuclear leukocytes. These results indicate that ibudilast inhibits anaphylactic bronchoconstriction which is considered to be largely mediated by endogenously released SRS-A. The inhibitory effect of ibudilast on anaphylactic bronchoconstriction in the presence of indomethacin is considered to be exerted through its antagonism to SRS-A.

Topics: Acetylcholine; Anaphylaxis; Animals; Arachidonate 5-Lipoxygenase; Asthma; Bronchoconstriction; Bronchodilator Agents; Calcimycin; Chromones; Guinea Pigs; Male; Neutrophils; Phospholipases A; Phospholipases A2; Platelet Activating Factor; Pyrazoles; Pyridines; SRS-A

Electrophysiological effects of anaphylactic stimulation of rat basophilic leukemia cells (RBL-2H3) were studied using conventional microelectrodes. Stimulation of passively sensitized cells by anti-immunoglobulin E resulted in hyperpolarization followed by depolarization. These changes in membrane polarization were associated with a decrease in input membrane resistance. No effect of anaphylactic stimulation was seen in Ca2+-free solution or when Ca2+ influx was blocked by Co2+, but it was mimicked by the Ca2+ ionophore A-23187. This suggests that the changes in ionic conductances were associated with calcium influx. These results support the hypothesis that membrane conductance changes are involved in the stimulus-secretion process of the RBL-2H3 cells.

Topics: Action Potentials; Anaphylaxis; Animals; Antigen-Antibody Reactions; Basophils; Calcimycin; Cell Line, Transformed; Cell Membrane; Immunoglobulin E; Leukemia, Experimental; Microelectrodes; Rats

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

A method is described for the isolation of mast cells from the mucosa of the small intestine of rats infected with the nematode Nippostrongylus brasiliensis. The cells release histamine on challenge with IgE-directed ligands and calcium ionophores but, in contrast to rat peritoneal mast cells, are refractory to the action of basic secretagogues. The mucosal and peritoneal cells also differ markedly in their sensitivity to particular anti-allergic drugs. These results further emphasize the functional heterogeneity of mast cells from different sources.

Topics: Anaphylaxis; Animals; Calcimycin; Cell Separation; Histamine; Histamine Release; Hookworm Infections; Immunoglobulin E; In Vitro Techniques; Intestinal Diseases, Parasitic; Intestine, Small; Mast Cells; Nippostrongylus; p-Methoxy-N-methylphenethylamine; Rats

Ro 21-7634 has previously been shown to inhibit histamine and SRS-A release from actively-sensitized guinea pig lung fragments upon antigen challenge. In the studies described herein, it was observed that Ro 21-7634 does not decrease SRS-A release but instead acts to inhibit the synthesis of this mediator. This was confirmed by studying SRS-A synthesis in vitro in rat peritoneal cells after challenge with ionophore A23187. In the peritoneal cell system, Ro 21-7634 exhibited an IC50 of 500 microM, in comparison with 5.8,11,14-eicosatetraynoic acid, phenidone and BW755C (IC50's of 2, 100, and 100 microM, respectively). When studied at 10(-4) and 10(-3) M in perfused guinea pig lung, Ro 21-7634 inhibited antigen-induced thromboxane A2 production by 68 and 96%, respectively. In this system, antigen is believed to induce thromboxane A2 production through the release of histamine and SRS-A from lung tissue. These mediators then interact at receptor sites in the lung parenchyma to induce thromboxane A2 synthesis. Ro 21-7634 could thus be inhibiting thromboxane A2 production by preventing the release of histamine and synthesis of SRS-A in the perfused lung system. Such a mechanism is suggested by the fact that although Ro 21-7634 was effective in inhibiting antigen-induced thromboxane production, it was ineffective in inhibiting thromboxane A2 production induced in the guinea pig lung system by the direct perfusion of histamine or SRS-A through the lung.

Topics: Airway Resistance; Anaphylaxis; Animals; Arachidonic Acid; Arachidonic Acids; Ascitic Fluid; Calcimycin; Guinea Pigs; Lung; Male; Muscle Contraction; Muscle, Smooth; Quinazolines; SRS-A; Thromboxanes

Platelet-activating factor (PAF) is a mediator of a anaphylaxis found initially in basophils and later in mouse and rat macrophages. The purpose of this paper was to determine the cellular origin of PAF released from human leucocytes and to establish if phagocytosis is a more important stimulus for PAF release than anaphylactic reactions. Phagocytic leucocytes (monocytes and PMNs) released PAF, physicochemically analogous to the PAF obtained by anaphylactic reactions in rabbits when challenged with zymosan, zymosan coated with complement, immune complexes, immunoglobulin aggregates or calcium ionophore A23187. Basophils failed to release PAF by anti-human IgE antibody, although positive degranulation and histamine liberaton were found. Pre-incubation of phagocytosing leucocytes with cytochalasin B or colchicine produced a diminution of PAF release, whereas beta-glucuronidase liberation was increased. The addition of carboxypeptidase B did not significantly modify PAF or beta-glucuronidase release. These data indicate that PAF obtained from preparations of human leucocytes comes from monocytes and polymorphonuclears; human basophils do not liberate measurable quantities of PAF, either by anaphylactic stimulus or by neutrophil cationic proteins; liberation of PAF and lysosomal content follow different mechanisms as they have different kinetics and are modified in an opposite way by drugs acting on the cytoskeleton.

Topics: Anaphylaxis; Antibodies, Anti-Idiotypic; Basophils; Blood Coagulation Factors; Calcimycin; Complement System Proteins; Humans; Leukocytes; Monocytes; Neutrophils; Phagocytosis; Platelet Aggregation; Zymosan

This report describes the immune release of a new mediator from human peripheral leukocytes, a basophil kallikrein-like activity (BK-A). The release process is initiated by the interaction of antigen on anti-IgE with cell-bound IgE, and appears to be similar in mechanism to the relase of histamine and other mediators of the immediate hypersensitivity reaction. The dose-response relationships and kinetics of histamine and BK-A release from antigen-challenged peripheral leukocytes are similar. The relase of the BK-A is calcium and temperature dependent, requires metabolic energy, and is controlled by hormone-receptor interactions that influence the cellular level of cyclic AMP, as has been described for other mediators of immediate hypersensitivity reactions. The data indicate that the interaction of BK-A with human plasma kininogen, generates immunoreactive kinin. We conclude that the antigen-IgE interation leads to the release from human basophils of a new mediator, a basophil kallikrein-like activity which may well be a link between reactions of immediate hypersenstivitity and the plasma and/or tissue kinin-generating systems.

Topics: Anaphylaxis; Antibodies; Arginine; Basophils; Bucladesine; Calcimycin; Colchicine; Deoxyglucose; Deuterium; Esterases; Histamine; Humans; Hypersensitivity, Immediate; Immunoglobulin E; In Vitro Techniques; Kallikreins; Kinetics; Leukocytes; Lymphocytes; Temperature; Theophylline

The divalent cation ionophore A23187 was found to produce a dose-dependent release of histamine from isolated mesenteric mast cells of the guinea pig. The process showed a specific requirement for calcium ions and was blocked by inhibitors of glycolysis. The effect of cAMP, theophylline, sympathomimetic amines and DSCG on the histamine release induced by the ionophore or by the antigen-antibody reaction was compared. In both cases, the release was inhibited by Bu2cAMP and by theophylline but higher concentrations were required with the ionophore. Adrenaline, isoprenaline and DSCG were effective only in the anaphylactic system. These results are compared with those previously reported for human leucocytes and rat peritoneal mast cells in which the release produced by the ionophore was found not to be inhibited by cAMP and its analogues. On the basis of these findings, the possible role of cAMP in the modulation of histamine release is discussed.

Topics: Anaphylaxis; Animals; Anti-Bacterial Agents; Calcimycin; Calcium; Cromolyn Sodium; Cyclic AMP; Guinea Pigs; Histamine Release; In Vitro Techniques; Mast Cells; Sympathomimetics; Theophylline

The mononuclear cells in peritoneal washings from normal rats can be induced to produce large amounts of slow reacting substance of anaphylaxis by incubation with 10 mM cysteine in the presence of the calcium ionophore A-23187. This production of slow reacting substance could be inhibited by the addition of non-steroidal anti-inflammatory drugs, e.g., indomethacin, ibuprofen and flurbiprofen, Furthermore, mediator production was inhibited by eicosatetraynoic acid, the substrate analog of arachidonic acid, and by 9,11-azoprosta-5, 13-dienoic acid (AZO analog 1), a structural analog of the prostaglandin endoperoxide, PGH2, which known to inhibit thromboxane synthesis. Relatively high concentrations of hydrocortisone acetate inhibited mediator production; this inhibition could be partly reversed by the addition of arachidonic acid or to a lesser extent by eicosatrienoic acid. Preliminary results suggest that a small fraction of the 3H-labled arachidonic acid which was taken up by these cells in vitro was associated with slow reacting substance. We postulate that slow reacting substance of anaphylaxis may be derived from a prostaglandin endoperoxide which is formed during the oxidation of arachidonic acid by the prostaglandin fatty acid cyclooxygenase.

Topics: Anaphylaxis; Animals; Anti-Inflammatory Agents; Arachidonic Acids; Autacoids; Calcimycin; Cells, Cultured; Hydrocortisone; Male; Peritoneum; Prostaglandin Antagonists; Prostaglandins; Rats

Topics: Anaphylaxis; Antigen-Antibody Reactions; Bucladesine; Calcimycin; Calcium; Cell Membrane Permeability; Cyclic AMP; Drug Synergism; Histamine Release; In Vitro Techniques; Mast Cells; Phosphatidylserines; Theophylline; Time Factors