Immunocytochemical analysis of cellular components in atherosclerotic lesions. Use of monoclonal antibodies with the Watanabe and fat-fed rabbit

Abstract

We have performed immunocytochemical investigations into the distribution of smooth muscle cells and macrophages in the atherosclerotic lesions of the Watanabe heritable hyperlipidemic (WHHL) and fat-fed rabbits. We used monoclonal antibodies specific for muscle cells and macrophages, the latter with a new macrophage-specific monoclonal antibody designated RAM11. Scattered macrophages were observed in the subendothelium in areas of grossly normal aorta. Raised lesions were divided into four major groups, based on qualitative aspects of cell localization: fatty streak, composed predominantly of macrophages; intimal thickening, composed predominantly of smooth muscle cells that displayed considerable morphological heterogeneity with an admixture of macrophages; early fibrous plaques, characterized by approximately equal numbers of smooth muscle cells and macrophages; advanced fibrous plaques, composed of a fibrous cap containing flat smooth muscle cells overlying a macrophage-rich zone of atheromatous debris. These studies demonstrate the nature of the lesions in the two rabbit models and the usefulness of monoclonal antibodies in analyzing the cellular composition of atherosclerotic lesions.