Studies of the Mechanisms of the Human Platelet Release Reaction Induced by Immunologic Stimuli

Abstract

Abstract Human platelets in the presence of plasma aggregate and release their granular contents when incubated with zymosan (Z), which can activate the C3 shunt. Under the same conditions other C3 shunt activators, inulin, endotoxin, and chemically aggregated immunoglobulin A had no effect on platelets. During preincubation with plasma at 37°C for 1 hr Z adsorbs plasma components such that it is active toward washed platelets. Formation of this activated Z (Z-X) was inhibited by cobra venom factor, hydrazine, heparin, EDTA (but not by EGTA), or by heating plasma at 50°C for 30 min. Combination of heat-treated and hydrazine-containing plasma restored the capacity to form Z-X. The third complement (C) component (C3) reactivated hydrazine-treated plasma. These characteristics suggest the involvement of the C3 shunt. Although an incubation temperature higher than 17°C was required for Z-X formation, factors which absorb to Z at 2°C and 17°C were also involved. Evidence was obtained that the 2°C factor was an immunoglobulin G (IgG) which, alone combined with Z, could cause an additional release reaction by the C independent mechanism. Z preincubated with serum had no effect on platelets although it activated C. Fibrinogen restored the ability of serum to form Z-X. The reaction of platelets with Z is discussed as a multi-site reaction involving IgG, C components and fibrinogen.