Human platelet IgG Fc receptor FcγRIIA in immunity and thrombosis

Arman, M.; Krauel, K.

Abstract

© 2015 International Society on Thrombosis and Haemostasis. 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 αIIbβ3 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.

Citation

Arman, M., & Krauel, K. (2015). Human platelet IgG Fc receptor FcγRIIA in immunity and thrombosis. Journal of thrombosis and haemostasis : JTH, 13(6), 893-908. https://doi.org/10.1111/jth.12905

• Journal Article Type: Review
• Acceptance Date: Mar 10, 2015
• Online Publication Date: Apr 21, 2015
• Publication Date: 2015-06
• Deposit Date: May 5, 2022
• Journal: Journal of Thrombosis and Haemostasis
• Print ISSN: 1538-7933
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 13
• Issue: 6
• Pages: 893-908
• DOI: https://doi.org/10.1111/jth.12905
• Keywords: Fc gamma receptor IIA; Immunity; Pathogens; Platelets; Thrombosis
• Public URL: https://hull-repository.worktribe.com/output/3571124