Ca++ antagonists and ACAT inhibitors promote cholesterol efflux from macrophages by different mechanisms. II. Characterization of intracellular morphologic changes.

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Abstract
The effects of the slow Ca++ channel blocker, nifedipine, and ACAT inhibitor, octimibate, on cholesterol-loaded macrophages were compared at the ultrastructural level. The Ca++ antagonist induced the formation of membrane-surrounded "lamellar bodies" originating from lysosomes. The macrophages secreted these lamellar bodies, which were rich in phospholipids and cholesterol, into the culture medium even in the absence of cholesterol acceptors. In contrast, the ACAT inhibitor induced the formation of lamellar bodies originating from lipid droplets, which were also surrounded by membranes. There is strong evidence that these latter membranes were newly synthesized at the margin of the lipid droplets by the endoplasmic reticulum. The lamellar bodies descending from lipid droplets after ACAT inhibitor treatment were not secreted by the cells. They were stored in the cytoplasmic compartment in the absence of high density lipoproteins (HDL). When HDL were added to the medium, the lamellar bodies specifically int...

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