Human platelet IgG Fc receptor Fc[gamma]RIIA in immunity and thrombosis

• Published in: Journal of thrombosis and haemostasis Vol. 13; no. 6; p. 893
• Main Authors: Arman, M, Krauel, K
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Limited 01.06.2015
• Subjects: Immune system; Medical research; Rodents; Thrombosis
• ISSN: 1538-7933; 1538-7836
• DOI: 10.1111/jth.12905

Summary Beyond their prominent role in hemostasis and thrombosis, platelets are increasingly recognized as having immunologic functions. Supporting this, human platelets express Fc[gamma]RIIA (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, Fc[gamma]RIIA 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 Fc[gamma]RIIA has received little attention in previous reviews on FcRs. This article summarizes and discusses the available information on human platelet Fc[gamma]RIIA. 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 Fc[gamma]RIIA 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 Fc[gamma]RIIA in IgG-independent hemostasis and physiologic thrombosis, by means of amplifying integrin [alpha]IIb[beta]3 outside-in signaling, has also been proposed. Nonetheless, the thrombotic complications found in some infective and autoimmune diseases may result from unbalanced Fc[gamma]RIIA-mediated platelet aggregation. Moreover, Fc[gamma]RIIA is not expressed in mice, and thrombocytopenia and/or thrombotic events found after drug administration can only be recapitulated by the use of human Fc[gamma]RIIA-transgenic mice. Altogether, the available data support a functional role for platelet Fc[gamma]RIIA in health and disease, and emphasize the need for further investigation of this receptor.