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 anticomplementa ry functions. Cobra venom a nticomplementary factor (CVF) inhibited LPS-platelet interaction, and the inhibition was both time and dose dependent. Doseresponse 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 antigenantibody complexes, zymosan, or heating at 56’ for 30 mm. 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.