Adhesion molecules on the endothelium and mononuclear cells in human atherosclerotic lesions.
Atherosclerotic lesions show features of a cell-mediated immune inflammatory process. From this viewpoint, the potential role of arterial endothelium in the recruitment of mononuclear cells (T lymphocytes and macrophages) was studied. The endothelium of diffuse intimal thickening (DIT) and atheromatous plaques (AP) in human coronary arteries and abdominal aortas was characterized for the expression of adhesion molecules ELAM-1, ICAM-1, and the major histocompatibility complex (MHC) class II antigens HLA-DR/DP. A marked increase in expression of ICAM-1 and ELAM-1, and to a lesser extent HLA-DR/DP was observed on endothelial cells that were adjacent to subendothelial infiltrates of T lymphocytes (CD3+, CD11a+, HLA-DR/DP+) and macrophages (CD14+, CD11a+, CD11c+, HLA-DR/DP+). This contrasted with a lower or absent expression of these activation markers at sites without prominent inflammatory cell infiltrates. These findings could be demonstrated in DIT as well as in AP. The observations suggest that cytokines produced by the subintimal infiltrates may activate the endothelium in a similar way as is observed in the microvasculature at sites of immune inflammation. The expression of these activation markers in the microvasculature is associated with enhanced leukocyte adhesion, permeability for macromolecules, and procoagulant activity, features known to occur also in early experimental atherosclerosis. The findings therefore support the concept that arterial endothelium plays an active role in the recruitment of mononuclear cells in atherosclerotic lesions.
D000328:Adult; D001012:Aorta, Abdominal; D001161:Arteriosclerosis / Q000378:metabolism* / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000032:analysis*; D003331:Coronary Vessels; D019040:E-Selectin; D004730:Endothelium, Vascular / Q000737:chemistry* / Q000473:pathology*; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D018799:Intercellular Adhesion Molecule-1; D008264:Macrophages / Q000737:chemistry* / Q000473:pathology; D008875:Middle Aged; D013601:T-Lymphocytes / Q000737:chemistry* / Q000473:pathology
D015815:Cell Adhesion Molecules; D019040:E-Selectin; D000949:Histocompatibility Antigens Class II; D018799:Intercellular Adhesion Molecule-1