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.
