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

Background FcγRIIA, a high-affinity receptor for IgG 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 α IIb β 3 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. Aims Assess 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 + ) as compared to 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 α IIb β 3 signaling.