Atheromatous and xanthomatous lesions contain macrophages laden with lipid, especially cholesteryl esters (1-4). The study of the cholesterol and lipoprotein metabolism

Atheromatous and xanthomatous lesions contain macrophages laden with lipid, especially cholesteryl esters (1-4). The study of the cholesterol and lipoprotein metabolism of these macrophages has not been extensively carried out because isolation and culture of these cells is difficult. Other sources of macrophages, including rodent peritoneal macrophages, have been investigated with particular emphasis on their ability to store cholesteryl ester, to degrade low-density lipoprotein (LDL), 1 and to detect the presence of a high-affinity receptor for LDL (5). Fibroblasts, smooth muscle cells, and circulating lymphocytes have been shown to have a high-affinity receptor specific for lipoprotein (6). The LDL receptor was first described by Brown and Goldstein, who showed that LDL was taken up by fibroblasts via the LDL receptor; LDL was then hydrolyzed in the lysosomes, releasing cholesterol to the cell. The cholesterol from LDL has three major regulatory functions in fibroblasts: (a) it inhibits endogenous cholesterol synthesis; (b) it stimulates cholesterol esterification; and (c) it inhibits LDL receptor synthesis (6). Macrophages used for the study of cholesterol and lipoprotein metabolism of phagocytic or scavenger cells have included rodent (5, 7-9) and canine (10) peritoneal macrophages and human monocyte-derived (HMD) macrophages (11, 12). Goldstein et al. (5) have shown that freshly isolated mouse peritoneal macrophages do not have LDL receptor activity, but more recently Mahley et al. (13) have reported that "incubation of mouse peritoneal macrophages for 24-48 h with lipoprotein-deficient serum leads to the expression of a small number of LDL receptors." Studies by Goldstein et al. of the cholesterol metabolism of mouse peritoneal macrophages using acetylated LDL (AcLDL), which has been chemically modified with acetic anhydride to have a negative charge (and thus is not recognized by the receptor for LDL [14]), have shown that AcLDL is actively degraded and the cells accumulated cholesteryl ester in response to incubation with AcLDL (5). Recently (12), we described a method for culturing H M D macrophages and showed that H M D macrophages not only degrade AcLDL but also have LDL receptor