Synergistic platelet activation by aggregates of IgG and the phospholipid platelet-activating factor 1-O-alkyl-2-acetyl-SN-glycero-3-phosphorylcholine

Immune complexes and 1-O-alkyl-2-acetyl-SN-glycero-3-phosphorylcholine (AGEPC) are potent platelet-activating factors which interact with distinct receptors on human platelets. The mechanisms of platelet activation by these two stimuli were investigated by examining the effects of AGEPC on human platelets which had been preexposed to IgG aggregates (IgG-Agg). AGEPC and IgG-Agg in combination activated platelet aggregation synergistically, whereas release of the granular constituent serotonin was not increased. Synergy was maximal within 1 min of exposure of platelets to IgG-Agg and persisted for 5 to 10 min after exposure to IgG-Agg. Synergy was observed at concentrations of IgG-Agg which release platelet granular constituents with minimal aggregation. Monomeric IgG, which did not activate platelets, did not augment the platelet response to AGEPC. Platelet activation by AGEPC is enhanced by both the granular constituent adenosine diphosphate (ADP) and by arachidonic acid, suggesting that one or both agents may contribute to synergy between AGEPC and IgG-Agg. Indomethacin inhibited granule release by IgG-Agg and enhancement of AGEPC-induced platelet aggregation by IgG-Agg. The ADP scavengers creatine phosphate/creatine phosphokinase also blocked synergistic platelet activation. These data suggest that IgG-Agg releases platelet granule ADP by a cyclooxygenase-dependent mechanism and the released ADP, in combination with AGEPC, activates platelets synergistically.