Human platelet IgG Fc receptor FcRIIA in immunity and thrombosis

Beyond their prominent role in hemostasis and thrombosis, platelets are increasingly recognized as having immunologic functions. Supporting this, human platelets express FcRIIA (CD32a), a low-affinity Fc receptor (FcR) for the constant region of IgG that recognizes immune complexes (ICs) and IgG-opsonized cells with high avidity. In leukocytes, FcRIIA engagement initiates strong effector functions that are key for immune and inflammatory responses, including cytokine release, antibody-dependent cell-mediated killing of pathogens, and internalization of ICs. However, the physiologic relevance of platelet-expressed FcRIIA has received little attention in previous reviews on FcRs. This article summarizes and discusses the available information on human platelet FcRIIA. The importance of this receptor in heparin-induced thrombocytopenia, a prothrombotic adverse drug effect, is well documented. However, studies demonstrating platelet activation by IgG-opsonized bacteria point to the physiologic relevance of platelet FcRIIA in immunity. In this context, platelet activation and secretion may facilitate both a direct antimicrobial function of platelets and crosstalk with other immune cells. Additionally, a role for platelet FcRIIA in IgG-independent hemostasis and physiologic thrombosis, by means of amplifying integrin (IIb3) outside-in signaling, has also been proposed. Nonetheless, the thrombotic complications found in some infective and autoimmune diseases may result from unbalanced FcRIIA-mediated platelet aggregation. Moreover, FcRIIA is not expressed in mice, and thrombocytopenia and/or thrombotic events found after drug administration can only be recapitulated by the use of human FcRIIA-transgenic mice. Altogether, the available data support a functional role for platelet FcRIIA in health and disease, and emphasize the need for further investigation of this receptor.