Inhibition of Endotoxic Lipopolysaccharide-mediated Platelet Aggregation by Cobra Venom Anticomplementary Factor

Aggregometry studies on endotoxic lipopolysaccharide (LPS)-mediated rabbit platelet aggregation were performed. Different preparations of LPS showed characteristic aggregometry profiles, and LPS with potent anticomplementary activities generally had a more vigorous platelet aggregation function than did LPS preparations with lesser anticomplementary functions. Cobra venom anticomplementary factor (CVF) inhibited LPS-platelet interaction, and the inhibition was both time and dose dependent. Dose-response curves of CVF inhibition on LPS or zymosan-mediated platelet aggregation were essentially identical. In vitro and in vivo studies showed that CVF inhibition persisted even when hemolytic complement activities reached more than 70% of those originally present. At the critical time of days 5 or 6 following CVF administration, the lack of platelet responses towards LPS could be restored by addition of fresh plasma from normal or C6-deficient rabbits, but not with plasma that had been treated with antigen— antibody complexes, zymosan, or heating at 56° for 30 min. The experimental data indicate that serum protein(s) other than the terminal complement components are involved in LPS-platelet interaction. It seems most likely that the factor(s) perturbed reside in the mechanisms involved in activation of the alternate pathway. Furthermore, it appears quite possible that LPS-platelet interactions can be inhibited by manipulating the humoral factor(s) involved rather than by altering the platelets themselves.