Apolipoprotein J (clusterin) induces cholesterol export from macrophage-foam cells: a potential anti-atherogenic function?
Apolipoprotein J (apo 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 complement activation, programmed cell death, tissue remodelling and lipid transport. 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 cholesterol and cholesteryl esters. Incubation of the foam cells with physiological concentrations of purified apo J led to a dose-dependent export of cholesterol. The appearance of cholesterol in the medium was associated predominantly with a decline in intracellular cholesteryl esters rather than intracellular free cholesterol. The kinetics of cholesterol release to apo J were similar to apo A-I, an established promoter of cholesterol efflux. Apo J was also shown to induce phospholipid efflux from cells, whereas the cholesterol exported to the medium was associated 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 evidence that apo J can promote cholesterol efflux from foam cells and indicates that it might have a function in cellular cholesterol homoeostasis in both normal and pathological situations.
Gelissen
I C
IC
Cell Biology Unit, Heart Research Institute, 145-147 Missenden Road, Camperdown, Sydney, N.S.W. 2050, Australia.
Hochgrebe
T
T
Wilson
M R
MR
Easterbrook-Smith
S B
SB
Jessup
W
W
Dean
R T
RT
Brown
A J
AJ
D000818:Animals; D001161:Arteriosclerosis / Q000378:metabolism* / Q000517:prevention & control; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D051152:Clusterin; D004305:Dose-Response Relationship, Drug; D005487:Foam Cells / Q000378:metabolism*; D006023:Glycoproteins / Q000494:pharmacology*; D006801:Humans; D017737:Macrophages, Peritoneal / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018832:Molecular Chaperones
C495242:CLU protein, human; C495243:Clu protein, mouse; D051152:Clusterin; D006023:Glycoproteins; D018832:Molecular Chaperones; D002784:Cholesterol