Immunocytochemical detection of Fc gamma receptors in human atherosclerotic lesions

Much evidence indicates that atherosclerotic lesions are largely of an infl ammatory nature. Activated macrophages and macrophage-derived foam cells la den with cholesterol esters are a major constituent of these lesions and ca n influence lesion formation via several potential mechanisms. One such mec hanism is Fc gamma receptor activation and/or Fc gamma receptor-mediated cl earance of immune complexes containing cholesterol, such as lipoprotein imm une complexes. That this mechanism contributes to lesion formation would be further supported if Fc gamma receptor expression in arterial lesions were demonstrated. We therefore used monoclonal antibodies and immunocytochemic al methods to analyze frozen sections of human arterial lesions for express ion of each of the three primary classes of mononuclear phagocyte Fc gamma receptors. Approximately 800 sections of aorta, carotid, and coronary arter ies obtained from five elderly donors were analyzed. The presence of macrop hages was determined by assaying reactivity of a monoclonal antibody specif ic to CD163, which is expressed only on cells of the human mononuclear phag ocyte lineage. Results indicate that highly cellular preatheromatous lesion s contained numerous macrophages in the zone of proliferation that expresse d each class of Fc gamma receptor (Fc gamma RIA, Fc gamma RIIA, and Fc gamm a RIIIA). Fc gamma receptor-positive cells were also present in medial and adventitial areas. Fc gamma receptor staining was both punctate and diffuse , the latter suggesting that soluble receptors were present in the extracel lular matrix. These data further support that Fc gamma receptor-mediated cl earance of immune complexes can occur in arterial lesions during atherogene sis. Expression of both the high affinity (Fc gamma RIA) and lower affinity (Fc gamma RIIAI Fc gamma RIIIA) receptors indicates that mono- and multiva lent IgG-containing immune complexes could engage Fc gamma receptors and in fluence lesion formation through several different inflammatory mechanisms triggered by receptor activation. (C) 2001 Elsevier Science B.V. All rights reserved.