Immunocytochemical detection of Fcγ receptors in human atherosclerotic lesions

Abstract Much evidence indicates that atherosclerotic lesions are largely of an inflammatory nature. Activated macrophages and macrophage-derived foam cells laden with cholesterol esters are a major constituent of these lesions and can influence lesion formation via several potential mechanisms. One such mechanism is Fcγ receptor activation and/or Fcγ receptor-mediated clearance of immune complexes containing cholesterol, such as lipoprotein immune complexes. That this mechanism contributes to lesion formation would be further supported if Fcγ receptor expression in arterial lesions were demonstrated. We therefore used monoclonal antibodies and immunocytochemical methods to analyze frozen sections of human arterial lesions for expression of each of the three primary classes of mononuclear phagocyte Fcγ receptors. Approximately 800 sections of aorta, carotid, and coronary arteries obtained from five elderly donors were analyzed. The presence of macrophages was determined by assaying reactivity of a monoclonal antibody specific to CD163, which is expressed only on cells of the human mononuclear phagocyte lineage. Results indicate that highly cellular preatheromatous lesions contained numerous macrophages in the zone of proliferation that expressed each class of Fcγ receptor (FcγRIA, FcγRIIA, and FcγRIIIA). Fcγ receptor-positive cells were also present in medial and adventitial areas. Fcγ receptor staining was both punctate and diffuse, the latter suggesting that soluble receptors were present in the extracellular matrix. These data further support that Fcγ receptor-mediated clearance of immune complexes can occur in arterial lesions during atherogenesis. Expression of both the high affinity (FcγRIA) and lower affinity (FcγRIIA/FcγRIIIA) receptors indicates that mono- and multivalent IgG-containing immune complexes could engage Fcγ receptors and influence lesion formation through several different inflammatory mechanisms triggered by receptor activation.