Lipid and Lipoprotein Research Group, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada T6G 2S2 Received July 12, 1991; Revised Manuscript Received October 29, 1991 abstract: Lipid microemulsion of phospholipid and triglyceride with the size of low-density lipoprotein was capable of removing cholesterol from cholesterol-loaded mouse peritoneal macrophages, resulting in reduction of intracellularly accumulated cholesteryl ester. Apolipoproteins (apo) AI, A-II, C-III, and E bound to the surface of the microemulsion did not modulate the interaction of the microemulsion with the cells in terms of the cholesterol efflux. The cholesterol removal by the microemulsion was enhanced by some 30% only when apoA-I,-A-II, and-E were present in excess to provide their free forms in the medium, but apoC-III did not show such an effect even by its excess amount. The kinetics including the results with apoC-III were consistent with a model that the apparent enhancement was due to generation of pre-ß high-density lipoprotein (HDL)-like particles upon the interaction of free apolipoproteins with macrophages [Hara, H., & Yokoyama, S.(1991) J. Biol. Chem. 266, 3080-3086], However, pre/3-HDL-like particle was not detected after 6-and 24-h incubation in the medium where cholesterol efflux to the emulsion was maximally enhanced by the apolipoproteins, and cholesterol and phospholipids removed from the cells were all found with the microemulsions. It was also shown separately that the lipids inpre/3-HDL-like particles generated by apoA-I and macrophages were rapidly, within the order of minutes, transferred to the apolipoprotein-covered microemulsions when they were incubated together. Thus, the data were consistent with a model that the free form of certainapolipoproteins, such as apoA-I,-A-II, and-Ebut not apoC-III, generates prejd-HDL-like particles with cellular lipids in situ and these particles act as mediators for cholesterol transfer from thecells to otherlipoproteins.

High-density lipoproteins (HDL) 1 or reconstituted HDL-like particles are known to be potent cholesterol acceptors when cholesterol-loaded cells are exposed to these lipoproteins in the medium in vitro (Werb & Cohn, 1971; Stein & Stein, 1973; Brown et al., 1980; Daniels et al., 1981; Rothblat & Phillips,