Platelet FcγRIIA is dispensable for hemostasis and arterial thrombosis in the absence of FcγRIIA-specific extracellular stimuli.

BACKGROUND: FcγRIIA, a high-affinity receptor for immunoglobulin G immune complexes with no ortholog in mice, has a prominent role in host defense against pathogens via immune cell activation. A role for platelet FcγRIIA in enhancing thrombosis was suggested, involving interplay between αIIbβ3 integrin and FcγRIIA, without requiring FcγRIIA-specific extracellular stimuli. Recent data challenged this view, showing that FcγRIIA inhibition neither impaired platelet spreading on fibrinogen nor prevented thrombus growth and stability under flow. OBJECTIVES: This study assessed contribution of FcγRIIA to platelet function and experimental hemostasis and thrombosis without FcγRIIA-specific trigger. METHODS: The role of FcγRIIA in platelet functions was evaluated using washed human platelets following blockade of FcγRIIA with the monoclonal antibody IV.3, and transgenic mice expressing human FcγRIIA (FcγRIIA+) when compared with wild-type (WT) mice. The importance of FcγRIIA in hemostasis and arterial thrombosis was assessed using a tail vein transection bleeding model and various thrombosis models with real-time intravital microscopy, respectively. RESULTS: Aggregation of washed human platelets to various agonists was identical in the absence or presence of IV.3, as was aggregation of washed WT and FcγRIIA+ platelets. Adhesive and aggregation properties of FcγRIIA+ and WT platelets were identical when perfused over collagen under flow. FcγRIIA+ and WT mice exhibited similar tail bleeding time and kinetic and extent of thrombus formation in various arterial thrombosis models. CONCLUSION: FcγRIIA does not contribute to platelet functions during hemostasis and arterial thrombosis in the absence of FcγRIIA-specific extracellular stimulation, which does not support a role for FcγRIIA in amplifying outside-in αIIbβ3 signaling.