LYSOSOMAL LIPID-ACCUMULATION FROM OXIDIZED LOW-DENSITY-LIPOPROTEIN ISCORRELATED WITH HYPERTROPHY OF THE GOLGI-APPARATUS AND TRANS-GOLGI NETWORK

Lipid accumulation within macrophages is a major sequelae of atheroscl erosis. Much of this lipid accumulation occurs within large, swollen l ysosomes. We analyzed lipid accumulation in cultured macrophages using oxidized or acetylated low density lipoprotein (LDL) as the loading a gent. Pigeon macrophages incubated for 48 h with mildly oxidized pigeo n LDL (TBARS = 5-10 nmol/mg protein) showed significant increases in c ellular cholesterol compared with untreated controls. Forty-eight perc ent of the increased cholesterol occurred as unesterified cholesterol. Treated cells had Lipid-swollen lysosomes similar to those of atheros clerotic foam cells. The increase in lysosomal lipid was accompanied ( correlation coefficient of 0.96) by increases in acid phosphatase stai ning cisternae of the Golgi and trans-Golgi network (TGN). THP-1 macro phages incubated with oxidized LDL showed similar lysosomal loading an d Golgi/TGN hypertrophy: In contrast, macrophages incubated with acety lated LDL accumulated significant amounts of cholesterol but the incre ase occurred as cholesteryl ester (81% in pigeons) within cytoplasmic droplets and there was no associated increase in acid phosphatase-cont aining cisternae of Golgi or TGN. The correlation in both pigeon and T HP-1 macrophages of oxidized LDL-induced lysosomal lipid accumulation and Golgi hypertrophy suggests a linkage of these two phenomena. This implicates intracellular membrane trafficking as a possible defect in foam cells of the atherosclerotic lesion.