Mediators of C5a-induced bronchoconstriction in the guinea pig.
Mediators of C5a-induced bronchoconstriction in the guinea pig.
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C5a 诱导豚鼠支气管收缩的介质。
DOI：
10.1159/000234459
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发表时间：
1987
期刊：
影响因子：
--
通讯作者：
Bell,RL
中科院分区：
文献类型：
--
作者：
Regal,JF;Bell,RL
本文观察了静脉注射C5a对麻醉、人工呼吸豚鼠肺阻力和动态肺顺应性的影响。从酵母菌激活的豚鼠血清中提纯了C5a和C5argade的混合物，称为C5a。静脉注射C5a引起剂量相关的支气管收缩，表现为顺应性下降和抵抗力增加。将混合物中的C5a转化为C5ade精氨酸羧肽酶B消化并没有显著改变支气管收缩的程度。药理拮抗剂被用来确定组胺、乙酰胆碱或花生四烯酸代谢产物是否是C5a诱导的支气管收缩的媒介。组胺H1拮抗剂吡拉明可抑制C5a引起的支气管收缩，提示组胺参与其中。胆碱能受体拮抗剂阿托品与吡咯胺联用可抑制C5a诱导的阻力增加，但不影响顺应性，提示乙酰胆碱在C5a诱导的支气管收缩中除了参与组胺诱导的支气管收缩之外，并不起主要作用。环氧合酶抑制剂吲哚美辛能够阻止C5a诱导的支气管收缩，提示花生四烯酸代谢产物参与了这一过程。由于吲哚美辛也可延缓白三烯C4(LTC4)诱导的支气管收缩，因此不能排除肽类优三烯参与C5a诱导的支气管收缩。对白三烯拮抗剂fPL-55712和L-649,923抑制LTC_4诱导的支气管收缩的特异性进行了评价。55712是非选择性的，因为它抑制前列腺素D2和组胺引起的支气管收缩以及LTC_4引起的支气管收缩。L-649,923只抑制LTC4引起的支气管收缩，而对C5a引起的支气管收缩无影响，提示肽类真核三烯不是C5a引起的支气管收缩的重要介质。用放射免疫法测定，在C5a诱导的支气管收缩过程中，血浆中肽类药物水平的变化与0。因此，这些研究对C5a诱导的动态肺顺应性降低和肺阻力增加进行了量化，并表明组胺和环氧合酶产物在C5a诱导的支气管收缩中起主要作用，而不是肽脑三烯。
The effect of intravenous injection of C5a on pulmonary resistance and dynamic lung compliance was determined in anesthetized, artificially respirated guinea pigs. A mixture of C5a plus C5ades argwas purified from yeast-activated guinea pig serum and is referred to as C5a. Intravenous injection of C5a caused a dose-related bronchoconstriction as evidenced by a decrease in compliance and increase in resistance. Conversion of the C5a in the mixture to C5ades argby carboxypeptidase B digestion did not significantly alter the magnitude of the bronchoconstriction. Pharmacological antagonists were employed to determine if histamine, acetylcholine or products of the arachidonate metabolism were mediators of C5a-induced bronchoconstriction. The histamine H1antagonist pyrilamine inhibited the C5a-induced bronchoconstriction, suggesting the involvement of histamine. The cholinergic receptor antagonist atropine in combination with pyrilamine caused an inhibition of the C5a-induced increase in resistance but not compliance, suggesting acetylcholine does not play a major role in C5a-induced bronchoconstriction beyond its known role in participating in histamine-induced bronchoconstriction. Involvement of arachidonate metabolites was suggested by the ability of the cyclooxygenase inhibitor, indomethacin, to prevent the C5a-induced bronchoconstriction. Because indomethacin also caused a delay in the leukotriene C4(LTC4)-induced bronchoconstriction, the participation of peptidoleukotrienes in the C5a-induced bronchoconstriction could not be ruled out. The leukotriene antagonists FPL 55712 and L-649,923 were evaluated for their specificity in inhibiting LTC4-induced bronchoconstriction. FPL 55712 was nonselective since it inhibited prostaglandin D2and histamine-induced bronchoconstriction as well as LTC4-induced bronchoconstriction. L-649,923 inhibited only the LTC4-induced bronchoconstriction and was without effect on the C5a-induced bronchoconstriction, suggesting that peptidoleukotrienes are not important mediators of C5a-induced bronchoconstriction. Using radioimmunoassay, the change in peptidoleukotriene levels detected in plasma during C5a-induced bronchoconstriction was not significantly different from 0. Thus, these studies have quantitated the C5a-induced decrease in dynamic lung compliance and increase in pulmonary resistance and suggest that histamine and cyclooxygenase products, but not peptidoleukotrienes, play a major role in C5a-induced bronchoconstriction.