Influence of high density lipoprotein on esterified cholesterol stores in macrophages and hepatoma cells
Liver Neoplasms, Experimental
The ability of high density lipoproteins (HDL) to induce the clearance of cholesteryl esters from cultured cells has been explored. Studies using the J774 mouse macrophage cell line showed that these cells are not stimulated to clear esterified cholesterol upon exposure to HDL. This was observed over a wide range of HDL concentrations (10 to 1000 micrograms/ml HDL protein), and the lack of stimulation was not influenced by a number of factors relating to the preparation of the HDL, such as HDL subfraction, varying extents of lecithin:cholesterol acyltransferase modification, or heparin-Sepharose chromatography to remove particles containing apo E. Neither the method of loading the cells with esterified cholesterol nor the physical state of the lipid droplets affected the inability of HDL to elicit esterified cholesterol clearance. In the presence of the acyl CoA:cholesterol acyltransferase inhibitor, Sandoz 58-035, where a high level of intracellular free cholesterol was generated, efflux of only a small fraction of the excess free cholesterol to HDL was observed. J774 cells were able to clear esterified cholesterol efficiently in the presence of cholesterol-free apolipoprotein HDL/phospholipid particles, indicating that the cells have the capacity to clear esterified cholesterol. Fu5AH hepatoma cells and P388.D1 mouse macrophage cells also failed to clear esterified cholesterol in response to HDL. In contrast, mouse peritoneal macrophages cleared esterified cholesterol efficiently to HDL, indicating that there are fundamental differences between mouse peritoneal macrophages and the other cells types studied in regard to cholesterol metabolism as influenced by HDL.