APOLIPOPROTEIN-J (CLUSTERIN) INDUCES CHOLESTEROL EXPORT FROM MACROPHAGE-FOAM CELLS - A POTENTIAL ANTI-ATHEROGENIC FUNCTION

Apolipoprotein J (ape J) is a secreted glycoprotein of which the exact function remains a matter for speculation. Apo J has been implicated in such diverse processes as sperm maturation, regulation of complemen t activation, programmed cell death, tissue remodelling and lipid tran sport. In this study a possible role for apo J in lipid transport was explored. Mouse peritoneal macrophages were incubated with acetylated low-density lipoprotein (AcLDL) to produce foam cells containing chole sterol and cholesteryl esters. Incubation of the foam cells with physi ological concentrations of purified apo J led to a dose-dependent expo rt of cholesterol. The appearance of cholesterol in the medium was ass ociated predominantly with a decline in intracellular cholesteryl este rs rather than intracellular free cholesterol. The kinetics of cholest erol release to apo J were similar to apo A-I, an established promoter of cholesterol efflux. Apo J was also shown to induce phospholipid ef flux from cells, whereas the cholesterol exported to the medium was as sociated with the apo J. Studies using foam cells from apo E-null mice showed that the cholesterol exported to the medium was independent of apo E production by the cells. These results present the first eviden ce that apo J can promote cholesterol efflux from foam cells and indic ates that it might have a function in cellular cholesterol homoeostasi s in both normal and pathological situations.