ROLE OF C3A/C5A IN ANTIGEN-INDUCED BRONCHOCONSTRICTION

在以前的研究中，我们已经表明，C5 a，第五个切割产物， 补体引起离体豚鼠气管的显著收缩 其由花生四烯酸代谢的产物（SRS-A）或多种产物介导。 拟议的研究旨在扩展这些先前的研究，以测试 假设补体第三组分裂解产物C3 a， 和/或C5 a引起豚鼠气管收缩和支气管收缩 通过与致敏豚鼠中抗原相同的一种或多种介质。 C3 a和C5 a将通过建立的方法从豚鼠血清中纯化 色谱程序。 抗原介导的气道变化 将在IgG型被动致敏的动物中研究口径 抗卵清蛋白以及仅用IgE型被动致敏的动物 抗卵清蛋白 使用蛋白A-Sepharose CL-4 B分离IgG和IgE 亲和色谱法，并将使用被动皮肤过敏反应进行测定。 将使用两种模型来检查气道口径的变化： 离体豚鼠气管平滑肌收缩和在体 吸入激发时肺阻力和动态顺应性的测量 在豚鼠身上。 将使用药物研究 组胺和花生四烯酸代谢产物在C5 a、C3 a和 抗原诱导的气管收缩和支气管收缩。 且此种 拮抗剂将被用来调查的作用， 组胺参与了反应。 抗原间交叉过敏反应 或C3 a/C5 a诱导的气管收缩和支气管收缩也将被抑制。 考察 如果拟议的研究结果表明，C3 a和/或C5 a 是抗原诱导的支气管收缩的可能介质， 类似的拮抗作用的药物，更长期的研究，然后 在抗原诱导的细胞中寻找C3 a和/或C5 a的形成 支气管收缩

In previous studies, we have shown that C5a, a cleavage product of the fifth complement, causes a significant contraction of the isolated guinea pig trachea which is mediated by a product (SRS-A) or products of arachidonate metabolism. The proposed research is intended to extend these previous studies to test the hypothesis that C3a, a cleavage product of the third component of complement, and/or C5a cause tracheal contraction and bronchoconstriction in the guinea pig via the same mediator or mediators as does antigen in sensitized guinea pigs. C3a and C5a will be purified from guinea pig serum by established chromatographic procedures. Mediators of antigen induced changes in airway caliber will be investigated in animals passively sensitized with IgG type anti-ovalbumin as well as animals passively sensitized with only IgE type anti-ovalbumin. IgG and IgE will be separated using protein A-Sepharose CL-4B affinity chromatography and will be assayed using passive cutaneous anaphylaxis. Two models for examining changes in airway caliber will be utilized: contraction of isolated guinea pig tracheal smooth muscle and in vivo measurements of lung resistance and dynamic compliance on inhalation challenge in the guinea pig. Pharmacological agents will be utilized to investigate the role of histamine and products of arachiodonate metabolism in C5a, C3a and antigen induced tracheal contraction and bronchoconstriction. In addition, such antagonists will be used to investigate the role of prostaglandins as modulators of histamine involvement in the responses. Crosstachyphylaxis between antigen or C3a/C5a induced tracheal contraction and bronchoconstriction will also be examined. If the results of the proposed studies indicate that C3a and/or C5a are possible mediators of antigen induced bronchoconstriction, by virtue of similar antagonism by pharmacological agents, more long term studies will then be conducted to look for the formation of C3a and/or C5a in antigen induced bronchoconstriction.