APOLIPOPROTEIN-B OF OXIDIZED LDL ACCUMULATES IN THE LYSOSOMES OF MACROPHAGES

We have studied the intracellular fate of the apolipoprotein B of copp er-oxidized LDL in cultured J774 macrophages, using subcellular fracti onation and immunofluorescence techniques. The oxidized apolipoprotein B, using cell fractionation, was located primarily in secondary lysos omes (identified using the lysosomal marker-enzyme aryl sulfatase). Li ght microscopy using antibodies to the mannose-6-phosphate receptor, t he lysosomal membrane protein lgp 120, and oxidized LDL (biotinylated) confirmed that apo B of oxidized LDL did accumulate in secondary lyso somes rather than in endosomes. We conclude from these results that th e oxidized apolipoprotein B of LDL reaches the secondary lysosomes, bu t is not efficiently degraded, leading to intracellular accumulation w ithin this compartment. If this occurs in vivo it may influence the ph ysiology of the macrophage and their subsequent roles in forming foam cells and the development of the fatty streaks of early atherosclerosi s.