title: Human platelet IgG Fc receptor FcγRIIA in immunity and thrombosis.
abstract: 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.
authors.affiliation: Centre for Cardiovascular Sciences, Institute of Biomedical Research, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
authors.forename: M
authors.initials: M
authors.lastname: Arman
authors.affiliation: Institut für Immunologie und Transfusionsmedizin, Universitätsmedizin Greifswald, Greifswald, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Krauel
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D001792:Blood Platelets / Q000276:immunology* / Q000378:metabolism*; D003141:Communicable Diseases / Q000097:blood / Q000276:immunology; D004195:Disease Models, Animal; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate; D007074:Immunoglobulin G / Q000097:blood* / Q000276:immunology*; D008024:Ligands; D008822:Mice, Transgenic; D015539:Platelet Activation; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D011487:Protein Conformation; D017452:Receptors, IgG / Q000097:blood* / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D013927:Thrombosis / Q000097:blood* / Q000235:genetics / Q000276:immunology*
chemical_list: C445323:FCGR2A protein, human; D007074:Immunoglobulin G; D008024:Ligands; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D017452:Receptors, IgG
keywords: Fc gamma receptor IIA; immunity; pathogens; platelets; thrombosis