The role of Fcγreceptors in atherosclerosis

Abstract

Atherosclerosis is widely considered to be an immune-mediated process. Fcγ receptors (Fcγ Rs) contribute to the regulation of a multitude of immune and inflammatory responses and are implicated in human atherosclerotic lesions. Major cell types involved in the pathogenesis of atherosclerosis express Fcγ Rs and their proatherogenic ligands such as immune complexes and C-reactive protein, which act to activate Fcγ R signaling pathways. This review summarizes recent significant progress addressing the multifaceted roles of Fcγ Rs in atherogenesis which comes from the studies of Fcγ R-deficient animal models, clinical investigations and in vitro molecular and cellular studies. These new findings help us appreciate the emerging role of Fcγ Rs in atherosclerosis, and suggest Fcγ Rs as a potential therapeutic target for atherosclerosis.

Role of C-reactive protein in osteoclastogenesis in rheumatoid arthritis

“…On monocytes and macrophages, CRP is mostly mediated by FcγR- dependent pathways. High-affinity receptor FcγRI (CD64) and low-affinity receptor FcγRIIA (CD32) are activating receptors, while low-affinity receptor FcγRIIB (CD16) is an inhibitory receptor [ 28 , 29 ]. CRP activates FcγRs, which phosphorylate immunoreceptor tyrosine-based activating motifs, causing the activation of Syk (spleen tyrosine kinase) and in turn initiating downstream signaling cascades [ 29 ].…”

“…High-affinity receptor FcγRI (CD64) and low-affinity receptor FcγRIIA (CD32) are activating receptors, while low-affinity receptor FcγRIIB (CD16) is an inhibitory receptor [ 28 , 29 ]. CRP activates FcγRs, which phosphorylate immunoreceptor tyrosine-based activating motifs, causing the activation of Syk (spleen tyrosine kinase) and in turn initiating downstream signaling cascades [ 29 ]. The interaction of CRP and FcγRs promotes survival and proliferation of macrophages and enhances the release of proinflammatory molecules through stimulation of MMPs, MCP-1, and M-CSF expression and inhibition of IL-10 secretion [ 30 - 34 ].…”

Biomarkers Related to Carotid Intima-Media Thickness and Plaques in Long-Term Survivors of Ischemic Stroke

“…Receptors for the Fc portion of immunoglobulin G (IgG), known as FcγRs, are the binding link between humoral and cellular immunologic reactions. Endothelial cells express FcγRs and pro-inflammatory mediators, such as immune complexes and C-reactive protein, that can activate FcγR-dependent pathways that lead to oxidative burst, degranulation, phagocytosis, cytokine production and antibody-dependent cell-mediated cytotoxicity (ADCC) [ 1 ]. The FcγRs are surface glycoproteins, encoded by eight genes located on chromosome 1q21–23.…”

“…Based on structural homology and differences in affinity for IgG, this family is divided into three subfamilies: FcγRI (CD64), FcγRII (CD32) and FcγRIII (CD16). FcγR isoforms can be activating receptors (FcRI, FcγRIIA and FcγRIII) or inhibitory receptors (FcγRIIB) [ 1 ]. Two studies have demonstrated associations between certain FcγRIIA polymorphisms and coronary artery disease (CAD) and ischemic stroke [ 2 , 3 ].…”