A PLASMA-LIPOPROTEIN CONTAINING ONLY APOLIPOPROTEIN-E AND WITH GAMMA-MOBILITY ON ELECTROPHORESIS RELEASES CHOLESTEROL FROM CELLS

Previous studies have identified lipid-poor high density lipoproteins with electrophoretic pre-beta-mobility as the initial accepters of cell-derived cholesterol in human plasma. These lipoproteins contain apolipoprotein A-I (apoA-I) as their sole apolipoprotein. In the present study, incubation of human plasma with [H-3]cholesterol-laden skin fibroblasts has led to the identification of another lipoprotein that serves as a potent initial acceptor of cell-derived cholesterol. This lipoprotein, which we term gamma-LpE, exhibits gamma mobility on agarose gel electrophoresis. As determined by nondenaturing PAGE and by electron microscopy, the size of the spherical particle ranges between 12 and 16 nm. SDS/PAGE and subsequent immunoblotting identified apoE as its sole apolipoprotein. Plasma from normal and apoA-I-deficient mice, but not from apoE deficient mice, released [H-3]cholesterol from fibroblasts into a gamma-migrating lipoprotein. Cell culture media from hepatoma cells or mouse peritoneal macrophages, both of which contain apoE of cellular origin, also promoted efflux of [H-3]cholesterol from fibroblasts into a gamma-migrating fraction. This was not observed with cell culture medium from fibroblasts alone. In conclusion, our results strongly indicate the presence in human plasma of a lipoprotein containing only apoE, gamma-LpE, which is secreted by peripheral cells and is a potent acceptor of cell-derived cholesterol,