Cholesteryl esterase-treated LDL augments oxidized LDL-mediated cholesteryl ester deposition in mouse peritoneal macrophages.
Arterial unesterified cholesterol, phospholipid particles have been isolated from atherosclerotic lesions and characterized. However, the role of these 'liposomes' in macrophage foam cell formation is unclear. Recently, LDL, after trypsin and cholesteryl esterase treatment (T/CE LDL), was shown to have physical properties similar to the unesterified cholesterol, phospholipid particles isolated from atherosclerotic lesions. Yet, when mouse peritoneal macrophages were incubated with these model particles in culture medium (DMEM and 5% LPDS), only an insignificant accumulation of cellular cholesteryl esters was observed. Previously, we demonstrated that complex formation between unesterified cholesterol, phosphatidylcholine liposomes and cupric sulfate-oxidized LDL dramatically enhances the ability of the liposomes to augment cellular cholesterol accretion (Greenspan P, Yu H, Mao F, Gutman RL. J Lipid Res 1997;38:101-109). When T/CE LDL, another cholesterol-rich phospholipid particle, was substituted for unesterified cholesterol phosphatidylcholine liposomes in our complex, mouse peritoneal macrophages accumulated a significant amount of both cellular unesterifed cholesterol (61 microg/mg cell protein) and cholesteryl esters (76 microg/mg cell protein) after 48 h of incubation. These results demonstrate again that the interaction of two cholesterol-bearing particles (T/CE LDL and oxidized LDL), which individually can not promote significant cholesterol accumulation in cells, will, when combined, produce macrophage foam cells.
Yu
H
H
Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens 30602, USA.
Gutman
R L
RL
Ryu
B H
BH
Greenspan
P
P
D000818:Animals; D002788:Cholesterol Esters / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004337:Drug Carriers; D005487:Foam Cells / Q000378:metabolism; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008081:Liposomes; D017737:Macrophages, Peritoneal / Q000378:metabolism*; D051379:Mice; D002787:Sterol Esterase / Q000378:metabolism*; D014357:Trypsin / Q000378:metabolism
D002788:Cholesterol Esters; D004337:Drug Carriers; D008077:Lipoproteins, LDL; D008081:Liposomes; C099252:oxidized low density lipoprotein; D002787:Sterol Esterase; D014357:Trypsin