Journal of Lipid Research, Vol 38, 101-109, Copyright © 1997 by Lipid Research, Inc.

ARTICLES

Cholesterol deposition in macrophages: foam cell formation mediated by cholesterol-enriched oxidized low density lipoprotein

P Greenspan, H Yu, F Mao and RL Gutman
Department of Pharmacology and Toxicology, College of Pharmacy, University of Georgia, Athens 30602-2356, USA.

Oxidized low density lipoprotein (LDL) is thought to mediate the transformation of macrophages to cholesterol-rich foam cells. Yet convincing evidence for this process is lacking in vitro. We suggest that oxidized LDL-mediated foam cell formation is not seen in vitro because the cholesteryl ester content of LDL particles (oxidized in the presence of transition metals) is dramatically reduced. Thus, if oxidized LDL could be cholesterol-enriched prior to its addition to macrophages, this lipoprotein would be made more capable of inducing the cellular deposition of cholesteryl esters. When we enriched cupric sulfate-oxidized LDL with cholesterol by incubation of this lipoprotein with unesterified cholesterol/phosphatidylcholine liposomes and added it to mouse peritoneal macrophage cultures, we found that: a) the enrichment of oxidized LDL with cholesterol did not alter the extent of oxidized LDL degradation; b) the cells accumulated massive amounts of cholesteryl ester (148 microg/mg cell protein) and unesterified cholesterol (260 microg/mg cell protein) after 24 h of incubation; and c) Sephacryl S-1000 chromatography of the cholesterol-enriched oxidized LDL verified the formation of large oxidized LDL-unesterified cholesterol/phosphatidylcholine complexes. These results demonstrate that oxidized LDL, when cholesterol-enriched, can mediate the formation of macrophage foam cells in culture
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				C. Whatling, H. Bjork, S. Gredmark, A. Hamsten, and P. Eriksson Effect of macrophage differentiation and exposure to mildly oxidized LDL on the proteolytic repertoire of THP-1 monocytes J. Lipid Res., September 1, 2004; 45(9): 1768 - 1776. [Abstract] [Full Text] [PDF]

				R. J. Cenedella, R. Jacob, D. Borchman, D. Tang, A. R. Neely, A. Samadi, R. P. Mason, and P. Sexton Direct perturbation of lens membrane structure may contribute to cataracts caused by U18666A, an oxidosqualene cyclase inhibitor J. Lipid Res., July 1, 2004; 45(7): 1232 - 1241. [Abstract] [Full Text] [PDF]

				P. G. Yancey and W. G. Jerome Lysosomal cholesterol derived from mildly oxidized low density lipoprotein is resistant to efflux J. Lipid Res., March 1, 2001; 42(3): 317 - 327. [Abstract] [Full Text]

				A. J. Brown, E. L. Mander, I. C. Gelissen, L. Kritharides, R. T. Dean, and W. Jessup Cholesterol and oxysterol metabolism and subcellular distribution in macrophage foam cells: accumulation of oxidized esters in lysosomes J. Lipid Res., February 1, 2000; 41(2): 226 - 237. [Abstract] [Full Text]

				P. G. Yancey and W. G. Jerome Lysosomal sequestration of free and esterified cholesterol from oxidized low density lipoprotein in macrophages of different species J. Lipid Res., July 1, 1998; 39(7): 1349 - 1361. [Abstract] [Full Text]

				W. G. Jerome, C. Cash, R. Webber, R. Horton, and P. G. Yancey Lysosomal lipid accumulation from oxidized low density lipoprotein is correlated with hypertrophy of the Golgi apparatus and trans-Golgi network J. Lipid Res., July 1, 1998; 39(7): 1362 - 1371. [Abstract] [Full Text]