Wg. Jerome et al., LYSOSOMAL LIPID-ACCUMULATION FROM OXIDIZED LOW-DENSITY-LIPOPROTEIN ISCORRELATED WITH HYPERTROPHY OF THE GOLGI-APPARATUS AND TRANS-GOLGI NETWORK, Journal of lipid research, 39(7), 1998, pp. 1362-1371
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.