PB0402 - The FcγRIIA receptor does not play a critical role in hemostasis and thrombosis in the absence of immune complexes

Background: FcγRIIA is a high-affinity receptor for immune complexes (ICs) expressed on human platelets and immune cells, whereas no corresponding ortholog is present in mice. FcγRIIA is primarily known for its role in host defense against pathogens through its ability to activate immune cells. A role for platelet FcγRIIA in experimental thrombosis has been suggested potentially involving a functional interplay between αIIbβ3 and FcγRIIA, the underlying mechanism remains however unclear, especially, in the absence of ICs.

Aims: To assess the contribution of FcγRIIA to platelet function and experimental models of hemostasis and thrombosis in absence of ICs.

Methods: The role of FcγRIIA in platelet adhesive and aggregation properties was evaluated using transgenic mice expressing human FcγRIIA (FcγRIIA+) as compared to wild-type (WT) mice that do not express FcγRIIA, and human platelets following blocking FcγRIIA with the monoclonal antibody IV.3. The importance of FcγRIIA in hemostasis and arterial thrombosis was assessed using a tail bleeding time assay and FeCl3-induced carotid injury coupled to real-time intravital microscopy.

Results: Aggregation of FcγRIIA+ platelets in response to ADP, collagen, CRP and U46619 was unchanged compared to WT platelets, as was the number of platelets adhering to immobilized fibrinogen under static conditions. The same results were obtained using human platelets in the absence or presence of IV.3. In addition, adhesive and aggregation properties of FcγRIIA+ and WT platelets were similar when perfused over immobilized collagen under arterial shear stress conditions. In vivo, FcγRIIA+ mice exhibited similar tail bleeding time as compared to WT mice. Finally, the extent of carotid artery thrombosis was unchanged between FcγRIIA+ and WT mice.

Conclusion(s): FcγRIIA does not play a role in amplification of αIIbβ3 outside-in signaling, and does not contribute to hemostasis and experimental thrombosis in the absence of ICs.