Stimler N P, Bloor C M, Hugli T E
Immunopharmacology. 1983 Feb;5(3):251-7. doi: 10.1016/0162-3109(83)90031-0.
The complement anaphylatoxin C3a from human or porcine serum contracts isolated peripheral airways from guinea pig in a manner which is independent of histamine release. In order to evaluate the role of arachidonic acid metabolites in the C3a response, dose-response curves for C3a-induced contractions of guinea pig lung strips were compared in the presence and absence of several inhibitors which block metabolism of arachidonic acid at relatively specific steps in the pathways. The inhibitor of leukotriene activity, FPL 55712, and the lipoxygenase inhibitor, nordihydroguiaretic acid (NDGA), had no significant effect on the tissue response to C3a alone or in combination with antihistamine. The cyclooxygenase inhibitors, indomethacin and aspirin, however, both resulted in significant inhibition, causing a shift in the C3a dose-response curve to higher concentrations. When the antihistamine, pyrilamine, was included with either indomethacin or aspirin, the C3a response was inhibited further, although pyrilamine alone had no effect. Thus, C3a-induced contractions of isolated lung parenchyma are mediated primarily by cyclooxygenase metabolites of arachidonic acid. This result is in contrast to the finding that C5a anaphylatoxin mediates lung tissue contraction by release of lipoxygenase metabolites of arachidonic acid.
来自人或猪血清的补体过敏毒素C3a可使豚鼠离体外周气道收缩，其方式独立于组胺释放。为了评估花生四烯酸代谢产物在C3a反应中的作用，在存在和不存在几种在相对特定的途径步骤中阻断花生四烯酸代谢的抑制剂的情况下，比较了C3a诱导的豚鼠肺条收缩的剂量反应曲线。白三烯活性抑制剂FPL 55712和脂氧合酶抑制剂去甲二氢愈创木酸（NDGA）对单独的C3a或与抗组胺药联合使用时的组织反应均无显著影响。然而，环氧化酶抑制剂吲哚美辛和阿司匹林均导致显著抑制，使C3a剂量反应曲线向更高浓度偏移。当抗组胺药吡苄明与吲哚美辛或阿司匹林一起使用时，C3a反应进一步受到抑制，尽管单独使用吡苄明没有效果。因此，C3a诱导的离体肺实质收缩主要由花生四烯酸的环氧化酶代谢产物介导。这一结果与C5a过敏毒素通过释放花生四烯酸的脂氧合酶代谢产物介导肺组织收缩的发现形成对比。
