ROLE OF C3A/C5A IN ANTIGEN-INDUCED BRONCHOCONSTRICTION

在以前的研究中，我们已经证明了C5a，一种第五种切割产物 补体，可引起豚鼠离体气管的显著收缩 这是由花生四烯酸代谢产物(SRS-A)介导的。 拟议的研究旨在扩展这些先前的研究，以测试 假设补体第三组分的裂解产物C3a， 和/或C5a引起豚鼠气管收缩和支气管收缩 通过与致敏豚鼠的抗原相同的一种或多种介体。 从豚鼠血清中提纯C3a和C5a 层析程序。抗原介体诱导的呼吸道改变 将在被动致敏的动物身上进行口径研究 抗卵清蛋白以及被动致敏的动物 抗卵清蛋白。用蛋白A-琼脂糖CL-4B分离免疫球蛋白和免疫球蛋白 亲和层析，并将采用被动皮肤过敏反应进行检测。 将使用两种模型来检查呼吸道口径的变化： 豚鼠离体气管平滑肌的收缩及在体收缩 吸入性激发时肺阻力和动态顺应性的测定 在豚鼠身上。将利用药理试剂来研究 组胺和花生四烯酸代谢产物在补体C5a、C3a和C3a中的作用 抗原引起气管收缩和支气管收缩。此外，这样的 拮抗剂将被用于研究前列腺素作为调节剂的作用。 组胺参与了这些反应。抗原之间的交叉免疫 或C3a/C5a引起的气管收缩和支气管收缩也会 检查过了。如果拟议研究的结果表明C3a和/或C5a 是抗原诱导的支气管收缩的可能介质，通过 类似的药理药物的拮抗作用，届时将进行更长期的研究 以寻找C3a和/或C5a在诱导的抗原中的形成 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.