Abstract
The cellular origin and development of early intimal lesions of rabbits fed a cholesterol diet for 8 to 12 weeks were studied morphologically and analyzed for several features of macrophage properties.
Scanning and transmission electron microscopic observations demonstrated a large number of circulating cells attached to the endothelial surface and the number of these which appeared to be migrating across the endothelium. Early fatty lesions were characterized by accumulations of fat-filled foam cells in the intima accompanied by appreciable numbers of blood-derived cells, notably monocytes, lymphocytes and polymorphonuclear leukocytes. Transitional sequences from the monocytes to the lipid-containing macrophages or foam cells were discerned. According to the method of Schaffner et al., foam cells were isolated from suspensions by substrate adherence to analyze the presence of authentic Fc and C3 receptors, immune or nonimmune phagocytic capacity, or to perform cytochemical examination. Easily dislodged plastic-adherent cells were filled with oil red O-positive granules and showed remarkable staining for nonspecific esterase. More than 90% of these plasticadherent cells had Fc receptors, whereas about 80% of them possessed C3 receptors. Attached erythrocytes were rapidly phagocytized. Ultrastructural observation of rosette-forming cells confirmed several features compatible with foam cells derived from macrophages. In addition, these cells exhibited phagocytosis of yeasts with or without pretreatment with normal rabbit serum. Among the cells migrating from the explants, a population of round cells revealed properties of macrophages such as positive nonspecific esterase activity, surface receptors, and phagocytosis of coated erythrocytes. The results indicate that foam cells, which characterize the early atherosclerotic plaques of cholesterol-fed rabbits, possess structural and functional properties of macrophages. It seems likely that circulating monocytes are the prime source of foam cells in the early phase of atherogenesis.
