Contribution of thromboxane A2 to the antigen-induced immediate asthmatic response mediated by IgG1 antibody by augmentation of bronchial responsiveness in guinea-pigs.
1. IgG1-mediated anaphylactic bronchoconstriction was elicited by intravenous administration of antigen to guinea-pig 2 days after passive sensitization with IgG1-rich serum, and this response was not affected by heating the serum (at 56 degrees C, for 4 h). IgE-mediated bronchoconstriction, provoked 14 days after passive sensitization with IgE-rich serum, was completely abolished by the heating of the serum. 2. S-1452 (10 mg kg-1, p.o.), a selective thromboxane (Tx) A2 antagonist, significantly but incompletely suppressed the IgG1-mediated bronchoconstriction, but did not affect the IgE-mediated one, while diphenhydramine (5 mg kg-1, i.v.), a histamine antagonist, almost completely inhibited both IgG1- and IgE-mediated bronchoconstriction. 3. Pretreatment with propranolol (1 mg kg-1, i.v.), a beta-adrenergic blocker, in addition to diphenhydramine, caused a long-lasting bronchoconstriction following antigen challenge in both animal models. This histamine-independent bronchoconstriction was markedly suppressed by S-1452 at a low dose of 0.1 mg kg-1. 4. A significant increase in bronchial responsiveness to i.v. acetylcholine (ACh), compared to the prechallenge value, occurred as early as 3 min and persisted for 24 h after antigen challenge in the IgG1 model, but was not observed in the IgE model. S-1452 (10 mg kg-1, p.o.) inhibited the IgG1-mediated bronchial hyperresponsiveness, as assessed 60 min after antigen challenge. 5. A marked elevation of TxB2 levels was observed in bronchoalveolar lavage fluid (BALF) 3 min after antigen challenge in the IgG1 model, while levels were not changed in the IgE model.(ABSTRACT TRUNCATED AT 250 WORDS)[1]References
- Contribution of thromboxane A2 to the antigen-induced immediate asthmatic response mediated by IgG1 antibody by augmentation of bronchial responsiveness in guinea-pigs. Arimura, A., Asanuma, F., Kurosawa, A., Harada, M. Br. J. Pharmacol. (1994) [Pubmed]
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