Analysis of the zymosan (Z)-induced human platelet response with washed platelets, fresh agammaglobulinemic plasma, and purified human IgG has identified a previously unrecognized role of IgG in this reaction, in addition to the previously reported requirements for C and fibrinogen. The rate-limiting step involves the assembly of C components on the Z particles and is independent of immunoglobulin. After the heat-labile components (supplied by agammaglobulinemic plasma) are Z bound, Z-specific IgG (apparently antibody) can bind to Z very rapidly, conferring on the previously inactive Z-complement-fibrinogen intermediate the capacity to induce platelet aggregation and serotonin release. The critical function of this Z-bound IgG appears to be in the interaction of the active Z complex with the platelet through Fc receptors, since soluble Fc fragments of each IgG subclass can totally block platelet activation. It is proposed that the human platelet requires a dual, or multi-site, stimulation to become activated during some forms of immunologic injury. These findings may provide some insight into clinical syndromes involving thrombocytopenia and intravascular coagulation during sepsis.
This work was supported in part, by Research Grant A1-12568 and Training Grant 5T32HL07152-02 from the United States Public Health Service, and by a grant from the Monroe County Chapter of the Arthritis Foundation.
Presented at the Annual Meeting of the American Federation for Clinical Research, Washington, D.C., May 2, 1977 (Clin. Res. 25:363A, 1977).