ARTERIAL FOAM CELLS WITH DISTINCTIVE IMMUNOMORPHOLOGIC AND HISTOCHEMICAL FEATURES OF MACROPHAGES

Abstract

A variable population of fat-filled foam cells in diet-induced experimental arterial intimal plaques of rabbits and monkeys were analyzed for several features characteristic of macrophages. These included the following: surface binding and phagocytosis of antibody-coated or complement-coated erythrocytes to detect specific surface receptors; cytochemical tests and ultrastructural features to evaluate cell function and structure; and rapid adherence to glass, a feature of macrophage activity, to isolate and identify a homogeneous population of fat-filled foam cells from excised and disrupted arterial lesions. Mixed populations of cells grown in culture from explants of lesions were analyzed; lipid-filled cells were studied in histologic sections of adjacent lesions. Of the easily dislodged glass-adherent cells from lesions, 80-90% had surface receptors for the Fc portion of IgG and for the 3rd component of complement. Coated red blood cells were readily phagocytized; noncoated cells were not. Acid lipase activity was demonstrated in the Fc-receptor-positive cells. These cells were devoid of ultrastructural features of smooth muscle. Among the cells growing or migrating out of explants, a population of large round foam cells possessed all of the macrophage features found in the glass-adherent cells from lesions and lacked ultrastructural characteristics of smooth muscle. Fusiform lipid vacuolated cells grew out of the explants but did not exhibit surface receptors, failed to phagocytize coated or noncoated erythrocytes and did not stain for acid lipase activity; these cells showed distinctive morphologic features of smooth muscle. In histologic sections of nearby lesions foam cells that showed macrophage characteristics, i.e., acid lipase activity and the presence of lysozyme-like antigen, lacked ultrastructural smooth muscle features. Smooth muscle cells in lesion sections often contained lipid but demonstrated no lysozyme or acid lipase activity. The occurrence of a population of cells with several functional and structural features of macrophages among the lipid-laden cells of experimental diet-induced arterial lesions suggests that some foam cells may not be of smooth muscle origin but may be derived from monocytes. That metabolically altered autochthonous arterial wall cells assume 1 or more characteristics of mononuclear phagocytes is less likely, since some of the markers used in these experiments are unrelated.