CHOLESTERYL ESTERASE-TREATED LDL AUGMENTS OXIDIZED LDL-MEDIATED CHOLESTERYL ESTER DEPOSITION IN MOUSE PERITONEAL-MACROPHAGES

Arterial unesterified cholesterol, phospholipid particles have been is olated from atherosclerotic lesions and characterized. However, the ro le 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 unesterifie d cholesterol, phospholipid particles isolated from atherosclerotic le sions. Yet, when mouse peritoneal macrophages were incubated with thes e model particles in culture medium (DMEM and 5% LPDS), only an insign ificant accumulation of cellular cholesteryl esters was observed. Prev iously, we demonstrated that complex formation between unesterified ch olesterol, phosphatidylcholine liposomes and cupric sulfate-oxidized L DL dramatically enhances the ability of the liposomes to augment cellu lar cholesterol accretion (Greenspan P, Yu H, Mao F, Gutman RL. J Lipi d Res 1997;38:101-109). When T/CE LDL, another cholesterol-rich phosph olipid particle, was substituted for unesterified cholesterol phosphat idylcholine liposomes in our complex, mouse peritoneal macrophages acc umulated a significant amount of both cellular unesterifed cholesterol (61 mu g/mg cell protein) and cholesteryl esters (76 mu g/mg cell pro tein) after 48 h of incubation. These results demonstrate again that t he interaction of two cholesterol-bearing particles (T/CE LDL and oxid ized LDL), which individually can not promote significant cholesterol accumulation in cells, will, when combined, produce macrophage foam ce lls. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.