Failure of exogenous apoprotein E-3 to enhance cholesterol egress from J-774 murine macrophages in culture.

HDL has been shown to enhance the removal of cholesterol from cultured fibroblasts, smooth muscle cells and macrophages, but fails to stimulate cholesterol removal from J-774 macrophages. Since J-774 macrophages do not synthesize or secrete apolipoprotein E, the effect of exogenous apolipoprotein E on HDL-mediated cellular cholesterol efflux was studied in this cell line. In cholesterol loaded J-774 macrophages total cellular cholesterol increased up to 6-7-fold, mainly cholesteryl esters. HDL3 removed up to 30% of total cellular cholesterol with a decrease in cholesteryl ester levels while free cholesterol levels remained unchanged. HDL3 was slightly superior to albumin in promoting cellular cholesterol removal. Exogenous apo E, over a wide range of apo E concentrations, did not enhance the ability of HDL3 to remove cellular cholesterol from cholesterol loaded J-774 cells. Exogenous apo E did not promote HDL-mediated cholesterol efflux from cells, thus suggesting a possible role for the intracellular route of newly synthesized apo E in these processes.