thromboxane-b2 and Hypersensitivity

Prostaglandins (PGs) are a family of lipid compounds that are derived from arachidonic acid via the cyclooxygenase pathway, and consist of PGD

Topics: Animals; Asthma; Humans; Hypersensitivity; Prostaglandins; Rhinitis, Allergic; Thromboxane B2

1. Sensitized guinea pig lungs release substantial amounts of prostaglandin E2, 6-keto-prostaglandin F1 alpha, thromboxane B2 and leukotrienes B4 and D4 upon challenge with the specific antigen. 2. A specific Platelet Activating Factor (PAF) antagonist (BN-52021) significantly inhibited the release of these mediators from anaphylactic lungs, suggesting the existence of interactions between PAF and eicosanoids. 3. The injection of PAF into unsensitized guinea pig lungs induced the release of prostaglandin E2, thromboxane B2 and leukotrienes B4 and D4 as well as spasmogens having contractile effects on the trachea, bronchus and parenchyma strips. 4. Our studies on the mechanism of action of PAF suggest that the actions of PAF are mediated by leukotriene B4 which in turn release thromboxane A2. Recent results suggest that similar interactions between PAF and eicosanoids are likely in immune-complex hypersensitivity reaction in the rat.

Topics: Animals; Arachidonic Acids; Dinoprostone; Diterpenes; Eicosanoic Acids; Enzyme Activation; Ginkgolides; Guinea Pigs; Hypersensitivity; Inflammation; Lactones; Leukotriene B4; Lung; Muscle Contraction; Phospholipases; Phospholipases A; Platelet Activating Factor; Prostaglandins E; SRS-A; Thromboxane B2

Asthma is a chronic inflammatory disorder of the airway and is characterized by airway remodeling, hyperresponsiveness, and shortness of breath. Modified Kushen Gancao Formula (mKG), derived from traditional Chinese herbal medicines (TCM), has been demonstrated to have good therapeutic effects on experimental allergic asthma. However, its anti-asthma mechanism remains currently unknown. In the present work, metabolomics studies of biochemical changes in the lung tissue and plasma of ovalbumin (OVA)-induced allergic asthma mice with mKG treatment were performed using ultra high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). Partial least squares-discriminate analysis (PLS-DA) indicated that the metabolic perturbation induced by OVA was reduced after mKG treatment. A total of twenty-four metabolites involved in seven metabolic pathways were identified as potential biomarkers in the development of allergic asthma. Among them, myristic acid (

Topics: Acetylcarnitine; Animals; Asthma; Biomarkers; Drugs, Chinese Herbal; Female; Hypersensitivity; Lung; Metabolome; Mice; Mice, Inbred BALB C; Myristic Acid; Sphingosine; Thromboxane B2

To observe the effect on infantile allergic cough with Minkeqing oral liquid (Minkeqing) and to study its cell molecular biologic mechanism.. The rat model was induced by inhalating ovalbumin; then the effects of Minkeqing on IL-6, IL-8, ET-1, TX-B2 in the blood and the bronchoalveolar lavage fluid (BALF) of the animal model were observed.. Minkeqing could reduce the levels of IL-6,IL-8,ET-1,Tx-B2 in the blood and BALF of the animal model.. Minkeqing has the significant function of inhibiting the release of inflammatory mediums.

Topics: Animals; Bronchoalveolar Lavage Fluid; Cough; Drug Combinations; Drugs, Chinese Herbal; Endothelin-1; Hypersensitivity; Interleukin-6; Interleukin-8; Male; Ovalbumin; Plants, Medicinal; Random Allocation; Rats; Rats, Wistar; Thromboxane B2

Nedocromil sodium, a disodium salt of a pyroquinolinedicarboxylic acid, raises the bronchial hyperresponsiveness threshold, because it inhibits the mediators released by the various cells, and reduces the involvement and activation of inflammatory cells. The aim of this study was to evaluate the state of activation of the immunocompetent cells and the main chemical mediators present in the bronchoalveolar lavage (BAL) fluid from 10 atopic asthmatic patients, before and after treatment with nedocromil sodium. The following examinations were performed before treatment and after 120 days of therapy with nedocromil sodium at 16 mg/day (two 2-mg puffs x 4): the level of chemical mediators and the state of activation of immunocompetent cells in BAL fluid; immunological analytes in activation of immunocompetent cells in BAL fluid; immunological analytes in peripheral blood; aspecific bronchial challenge test with ultrasonicated bidistilled H2O fog to evaluate variations in the hyperreactivity threshold; questionnaire to determine any adverse effects of treatment (cough, breathlessness, sleep disorders). Our findings demonstrate that nedocromil sodium prevents the release of chemotactic and inflammatory mediators by the effector cells and thus stabilizes microvascular permeability and epithelial damage, so raising the threshold of response to bronchoconstriction stimuli. Lastly, nedocromil sodium is associated with a better preventive therapeutic efficacy and good tolerance and can therefore be suggested as a valid drug to be used in the long-term treatment of bronchial asthma.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Albumins; Asthma; Blood Proteins; Bronchial Hyperreactivity; Bronchial Provocation Tests; Bronchoalveolar Lavage Fluid; Dinoprostone; Eosinophil Granule Proteins; Humans; Hypersensitivity; Immunoglobulins; Immunologic Factors; Leukocytes; Leukotriene B4; Lymphocytes; Macrophages; Male; Nedocromil; Peptide Hydrolases; Ribonucleases; Thromboxane B2

Bronchoconstriction (BC) is the main feature of anaphylaxis in the guinea pig. Since LPS induces lung inflammation and antigen-induced BC depends on the endogenous formation of histamine and arachidonate metabolites, we studied whether LPS might modulate antigen-induced BC. Guinea pigs were sensitized subcutaneously with 10 micrograms ovalbumin (OA) on days 0 and 14. LPS (100 micrograms/kg) was injected intravenously on day 21, and daily injections of LPS were continued before the antigenic challenge on day 22, 23, 24, or 25. Intratracheal injection of 100 micrograms OA induced an abrupt and reversible BC. Single or repetitive injections of LPS reduced BC. LPS is likely to reduce the OA-induced BC by affecting the histamine-dependent component of BC, since (a) LPS induced a partial degranulation of lung mast cells; (b) BC is reduced by mepyramine, an histamine receptor antagonist; (c) LPS did not affect BC in mepyramine-treated guinea pigs; (d) LPS reduced histamine release by OA-stimulated guinea pig lungs in vitro. Moreover, the in vitro OA-induced production of arachidonate metabolites was also reduced by LPS. The decreased formation of TXB2 was not only secondary to a reduced release of histamine, since LPS inhibited TXB2 formation in the presence of mepyramine. Finally, the FMLP-induced BC and mediator release were inhibited by LPS, whereas the platelet activating factor-induced pulmonary responses were not. Thus, the protective effect of LPS is not antigen-specific and does not result from a general desensitization. These studies indicate that a single dose of LPS reduces the antigen-induced BC by reducing histamine release from lung mast cells, although a decreased formation of eicosanoids may contribute to the protective effect of LPS.

Topics: Animals; Antigens; Aspirin; Bronchoconstriction; Cell Degranulation; Endotoxins; Escherichia coli; Guinea Pigs; Hemodynamics; Histamine; Hypersensitivity; Leukopenia; Lipopolysaccharides; Mast Cells; Microscopy, Electron; N-Formylmethionine Leucyl-Phenylalanine; Ovalbumin; Platelet Activating Factor; Pyrilamine; Thromboxane B2

The development of an allergic bronchoconstriction model in rats is described. In actively sensitized Donryu strain rats, there was a remarkable biphasic increase in airway resistance within 10 min after antigen challenge on day 9 to day 21. The increase in airway resistance, correlated with the IgE titer and the dose of antigen, was inhibited by disodium cromoglycate (DSCG) or by aminophylline. This bronchoconstriction was remarkably blocked by methysergide (25 and 100 micrograms/kg) while pyrilamine inhibited it partially at the same dose. Serotonin (greater than 30 micrograms/kg) but not histamine (less than 1,000 micrograms/kg) induced a bronchoconstriction. FPL-55712 (1,10 mg/kg) inhibited it significantly. The content of thromboxane B2 (TxB2) in plasma increased during the bronchoconstriction while the content of peptide-leukotrienes (p-LTs) in plasma did not increase significantly. OKY-046 inhibited not only allergic bronchoconstriction but also the increase in TxB2 levels in plasma. The late phase of the bronchoconstriction was more susceptible to OKY-046. In conclusion, this model seems to be useful for the screening of antiasthma drugs because of a relationship with the dose of antigen, IgE titer and the susceptibility to an antiallergic drug or a bronchodilator. It is demonstrated that the major part of this allergic bronchoconstriction depends on serotonin, and it is also suggested that thromboxane A2 may play an important role in the late phase of the bronchoconstriction.

Topics: Airway Resistance; Allergens; Aminophylline; Animals; Bronchial Spasm; Chromones; Cromolyn Sodium; Dose-Response Relationship, Immunologic; Histamine; Hypersensitivity; Leukotrienes; Male; Methacrylates; Methysergide; Pyrilamine; Rats; Rats, Inbred Strains; Serotonin; Thromboxane B2; Time Factors

A number of food additives and industrial chemicals, responsible for inducing symptoms of intolerance in some individuals, have been studied in tests measuring platelet activation by noradrenaline. All the investigated agents inhibited platelet aggregation and this was associated with inhibition of the cyclo-oxygenase-thromboxane pathway. Suboptimal inhibitory concentrations of the agents studied had additive inhibitory effects on platelet aggregation when they were tested in pairs, or when tested with salicylate or aspirin. The results support the theory that some food additives and industrial chemicals induce intolerance because of their aspirin-like properties.

Topics: Adolescent; Adult; Aspirin; Blood Platelets; Cyclooxygenase Inhibitors; Female; Food Additives; Humans; Hypersensitivity; Male; Middle Aged; Pharmaceutic Aids; Phthalic Anhydrides; Platelet Aggregation; Platelet Aggregation Inhibitors; Sulfites; Thromboxane B2

Sulfidopeptide leukotrienes (LTs) C4, D4 and E4 are important mediators in the pathophysiology of bronchial asthma. Sch 37224, 1-(1,2-dihydro-4-hydroxy-2-oxo-1-phenyl-1,8-naphthyridin-3-yl) pyrrolidinium, hydroxide inner salt, has been found to inhibit the formation of these autocoids. Although Sch 37224 did not inhibit 5-lipoxygenase, cyclooxygenase or phospholipase A2, it inhibited LTD4 and thromboxane B2 release by anaphylactic guinea pig lung (IC40 = 3.9 and 1.9 microM, respectively). At 5 microM Sch 37224 also inhibited superoxide anion radical generation from activated human polymorphonuclear neutrophilic leukocytes. When administered p.o. to guinea pigs, Sch 37224 decreased a LT-mediated allergic bronchospasm (ED40 = 1.1 mg/kg) for 6 hr and did not exhibit tolerance. In addition to its activities in allergen-induced bronchospasm in guinea pigs, Sch 37224 also inhibited hyperventilation-induced bronchospasm in guinea pigs at 0.5 to 5 mg/kg and anaphylactic bronchospasm in rats at 0.1 to 10 mg/kg. Sch 37224 was weak or ineffective as an antagonist of histamine, methacholine, serotonin, LTC4 or platelet activating factor induced bronchospasms in guinea pigs. Also, Sch 37224 was not a bronchodilator or calcium influx blocker and had only weak relaxant activity on guinea pig trachea in vitro (IC40 = 51 microM). Sch 37224 is, therefore, a potential antiallergic agent that inhibits LT release. It is p.o. effective in animal models of allergic and nonallergic-mediated bronchospasms.

Topics: Animals; Arachidonic Acid; Arachidonic Acids; Bronchi; Bronchial Spasm; Guinea Pigs; Histamine H1 Antagonists; Histamine Release; Hypersensitivity; In Vitro Techniques; Leukotriene Antagonists; Leukotrienes; Male; Naphthyridines; Rats; Thromboxane B2

In order to test the hypothesis that alveolar macrophages (AM) from asthmatics might manifest abnormalities in the amounts, spectrum, or glucocorticoid regulation of eicosanoid synthesis, we compared arachidonic acid (AA) metabolism under resting and ionophore A23187-stimulated conditions in cultured AM obtained by bronchoalveolar lavage from 10 asthmatic, nine atopic, and 10 nonatopic normal subjects. [14C]AA-prelabeled AM constitutively released free [14C]AA and release increased significantly with A23187 incubation. Under resting conditions, unlabeled cells produced small amounts of immunoreactive thromboxane B2 (TxB2), prostaglandin D2 (PGD2), prostaglandin E2 (PGE2), and leukotriene B4 (LTB4). With A23187 stimulation there were significant increases in the synthesis of all immunoreactive metabolites, which were produced in the following relative amounts: LTB4 much greater than TxB2 greater than PGD2 greater than leukotriene C4 greater than PGE2. High performance liquid chromatographic separation of radiolabeled eicosanoids produced by prelabeled cells confirmed the radioimmunoassay results and further indicated the production of relatively large amounts of 5-hydroxyeicosatetraenoic acid and 12-hydroxyheptadecatrienoic acid. Pretreatment (16 h) with 1 microM methylprednisolone inhibited A23187-induced synthesis of immunoreactive cyclooxygenase products to a greater extent than immunoreactive leukotrienes. We identified no significant differences among the three study groups in the quantities or profiles of eicosanoids synthesized either constitutively or with A23187 stimulation, nor in their regulation by methylprednisolone.

Topics: Adolescent; Adult; Arachidonic Acid; Arachidonic Acids; Asthma; Bronchoalveolar Lavage Fluid; Bronchoscopy; Cells, Cultured; Chromatography, High Pressure Liquid; Humans; Hypersensitivity; Leukotrienes; Macrophages; Methylprednisolone; Prostaglandins; Pulmonary Alveoli; Reference Values; Thromboxane B2

By comparison with ventricular tissues, collagenase-dispersed cell suspensions obtained from atrial tissues of sensitized guinea-pigs showed a higher histamine content, a higher proportion of mast cells, and a higher release with antigen or antisera to IgG, IgG1 and IgG2 of the following mediators: histamine, thromboxane B2 and leukotriene C4.

Topics: Animals; Cardiomyopathies; Guinea Pigs; Heart Atria; Heart Ventricles; Histamine Release; Hypersensitivity; Mast Cells; Myocardium; SRS-A; Thromboxane B2

Amoxanox has potent antiallergic activity because it inhibits the release of chemical mediators such as histamine and leukotrienes. We studied the in vitro effect of amoxanox on arachidonic acid metabolism, including the lipoxygenase and cyclooxygenase pathways. Amoxanox inhibited calcium ionophore A23187-induced formation of 5-HETE, LTB4, SRS-A (LTC4, LTD4 and LTE4), and 12-HETE in rat peritoneal resident monocytes. These results indicate that amoxanox inhibits 5- and 12-lipoxygenases. The compound, however, did not affect the formation of TXB2 or 6-keto-PGF1 alpha in guinea pig lung fragments and PGE2 or PGF2 alpha in bovine seminal vesicles, suggesting that it did not inhibit cyclooxygenase. These results show that the antiallergic action of amoxanox is associated, at least in part, with the reduction of leukotrienes due to the inhibition of lipoxygenases.

Topics: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; 5,8,11,14-Eicosatetraynoic Acid; Aminopyridines; Animals; Asthma; Calcimycin; Cattle; Guinea Pigs; Histamine H1 Antagonists; Hydroxyeicosatetraenoic Acids; Hypersensitivity; In Vitro Techniques; Leukotriene B4; Lipoxygenase Inhibitors; Lung; Male; Monocytes; Prostaglandins; Rats; Rats, Inbred Strains; SRS-A; Thromboxane B2

Calves given 2 subcutaneous inoculations (4 ml, 4.5 weeks apart) of an inactivated bluetongue virus serotype 17 (BTV-17), aluminum hydroxide adjuvant, and cimetidine (600 mg) or levamisole (819 mg, 6 ml) combination were challenge exposed with virulent BTV-17 (2.5 x 10(5) embryo lethal dose) 9 weeks after the 1st inoculation and were monitored for 35 days. Plasma prostaglandins (PG) and thromboxane (Tx) B2 were measured by radioimmunoassay. Histamine was assayed spectrofluorometrically. During the inoculation period (9 weeks from the 1st inoculation to challenge exposure) PGE and histamine increased from base-line concentrations of 34 +/- 3 pg/ml and 1.2 +/- 0.1 ng/ml to 83 +/- 8 pg/ml and 2.0 +/- 0.1 ng/ml, respectively, whereas PGF2 alpha decreased from base-line values of 356 +/- 41 pg/ml to 226 +/- 16 pg/ml. Significant (P less than or equal to 0.05) changes from base-line TxB2 values (110 +/- 7 pg/ml) were not observed during the inoculation period. After challenge exposure, maximum increases were observed in TxB2 (157 +/- 10 pg/ml), PGF2 alpha (713 +/- 93 pg/ml), PGE (140 +/- 30 pg/ml), and histamine (3.6 +/- 0.2 ng/ml) concentrations at 4, 7, 7, and 14 days after challenge exposure, respectively. Concentrations of PGF2 alpha and TxB2 decreased from base-line values to 211 +/- 42 pg/ml and 75 +/- 11 pg/ml, respectively, 21 days after challenge exposure and then returned to base-line values. Significant changes were not observed in plasma concentrations of 6-keto-PGF1 alpha. Results indicate that PG, TxA2, and histamine may be involved in the hypersensitivity reaction to BTV in cattle.

Topics: Animals; Bluetongue; Bluetongue virus; Cattle; Cattle Diseases; Cimetidine; Histamine; Hypersensitivity; Levamisole; Prostaglandins; Sheep; Thromboxane A2; Thromboxane B2; Thromboxanes

Topics: Animals; Arachidonic Acid; Arachidonic Acids; Guinea Pigs; Hypersensitivity; In Vitro Techniques; Indomethacin; Kinetics; Lung; Male; Microsomes; Ovalbumin; Prostaglandin-Endoperoxide Synthases; Thromboxane B2; Time Factors

The effects of Metformin treatment on platelet responsiveness to aggregating agents was studied in cholesterol-fed rabbits. Three groups of animals were fed, for one month, either a normal (N), or a hypercholesterolemic (HC), or a hypercholesterolemic + 0.5% Metformin diet (HC + Met), Platelets from the HC rabbits required significantly lower collagen and arachidonic acid concentrations to aggregate, as compared to platelets from N rabbits. The platelet response from the HC + Met rabbits was not significantly different from that of normals. The cholesterol/phospholipid ratio in platelets was increased in both dietary groups (HC, HC + Met). The serum thromboxane B2 concentrations did not show any significant difference between the groups. Plasma exchange experiments failed to indicate a specific effect of the plasma environment on platelet behaviour. In view of the inactivity of metformin on the platelet cyclo-oxygenase pathway, the reported results suggest that metformin may act by an as yet unexplored mechanism.

Topics: Animals; Blood Platelet Disorders; Blood Platelets; Cholesterol, Dietary; Collagen; Hypercholesterolemia; Hypersensitivity; Lipids; Male; Metformin; Plasma Exchange; Platelet Aggregation; Rabbits; Thromboxane B2