Beyond their prominent role in hemostasis and thrombosis, platelets are increasingly recognized as having immunologic functions. Supporting this, human platelets express FcγRIIA (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, FcγRIIA 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 FcγRIIA has received little attention in previous reviews on FcRs. This article summarizes and discusses the available information on human platelet FcγRIIA. 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 FcγRIIA 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 FcγRIIA in IgG-independent hemostasis and physiologic thrombosis, by means of amplifying integrin αII b β3 outside-in signaling, has also been proposed. Nonetheless, the thrombotic complications found in some infective and autoimmune diseases may result from unbalanced FcγRIIA-mediated platelet aggregation. Moreover, FcγRIIA is not expressed in mice, and thrombocytopenia and/or thrombotic events found after drug administration can only be recapitulated by the use of human FcγRIIA-transgenic mice. Altogether, the available data support a functional role for platelet FcγRIIA in health and disease, and emphasize the need for further investigation of this receptor.
Keywords: Fc gamma receptor IIA; immunity; pathogens; platelets; thrombosis.
© 2015 International Society on Thrombosis and Haemostasis.