Complement and Arachidonic Acid Transformation

We have found that complement is activated during blood coagulat ion (1). This activation was characterized by the development of ultrastructural lesions on the platelet surface subsequent to physiologic clotting. The appearance of the lesions was dependent on the presence of thrombin and of C3. In further studies, the role of complement in thrombin-media ted platelet function was investigated (2, 3). It was found that thrombin-media ted platelet aggregation and release of serotonin was significantly enhanced in the presence of complement. Only complement components C3, C5, C6, C7, C8, and C9 were required for this reactivity. No known activating mechanism of either the classical pa thway or alternative pa thway was required. Thus, a new pa thway of activation of complement was descr ibed--one which required thrombin, the platelet surface, and entered the known complement sequence at the C3 stage. Activation of this pa thway led to the product ion of C5b-9 complexes that were visualized as typical lesion formation on the platelet surface (3). Dur ing these studies it was shown that the complement effect was inhibited by aspirin and indomethacin, drugs known to inhibit platelet cyclooxygenase. Thus the possibility existed that the complement effect might be mediated via the arachidonic acid transformation pa thway with product ion of thromboxane A2. The purpose of this study was to elucidate the role of complement in the arachidonic acid transformation pa thway in platelets.