HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dhaliwal, B. S. Articles by Steinbrecher, U. P. Search for Related Content PubMed PubMed Citation Articles by Dhaliwal, B. S. Articles by Steinbrecher, U. P. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol. 41, 1658-1665, October 2000
Copyright © 2000 by Lipid Research, Inc.

Original Article

Cholesterol delivered to macrophages by oxidized low density lipoprotein is sequestered in lysosomes and fails to efflux normally

Correspondence to: Urs P. Steinbrecher

Oxidized low density lipoprotein (LDL) has been found to exhibit numerous potentially atherogenic properties, including transformation of macrophages to foam cells. It is believed that high density lipoprotein (HDL) protects against atherosclerosis by removing excess cholesterol from cells of the artery wall, thereby retarding lipid accumulation by macrophages. In the present study, the relative rates of HDL-mediated cholesterol efflux were measured in murine resident peritoneal macrophages that had been loaded with acetylated LDL or oxidized LDL. Total cholesterol content of macrophages incubated for 24 h with either oxidized LDL or acetylated LDL was increased by 3-fold. However, there was no release of cholesterol to HDL from cells loaded with oxidized LDL under conditions in which cells loaded with acetylated LDL released about one-third of their total cholesterol to HDL. Even mild degrees of oxidation were associated with impairment of cholesterol efflux. Macrophages incubated with vortex-aggregated LDL also displayed impaired cholesterol efflux, but aggregation could not account for the entire effect of oxidized LDL. Resistance of apolipoprotein B (apoB) in oxidized LDL to lysosomal hydrolases and inactivation of hydrolases by aldehydes in oxidized LDL were also implicated. The subcellular distribution of cholesterol in oxidized LDL-loaded cells and acetylated LDL-loaded cells was investigated by density gradient fractionation, and this indicated that cholesterol derived from oxidized LDL accumulates within lysosomes.

Thus impairment of cholesterol efflux in oxidized LDL-loaded macrophages appears to be due to lysosomal accumulation of oxidized LDL rather than to impaired transport of cholesterol from a cytosolic compartment to the plasma membrane. — Dhaliwal, B. S., and U. P. Steinbrecher. Cholesterol delivered to macrophages by oxidized low density lipoprotein is sequestered in lysosomes and fails to efflux normally. J. Lipid Res. 2000. 41: 1658;–1665.

Supplementary key words: macrophages, oxidized LDL, foam cells, cholesterol efflux, lysosomes

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				G. Murphy Jr., R. L. Rouse, W. W. Polk, W. G. Henk, S. A. Barker, M. J. Boudreaux, Z. E. Floyd, and A. L. Penn Combustion-Derived Hydrocarbons Localize to Lipid Droplets in Respiratory Cells Am. J. Respir. Cell Mol. Biol., May 1, 2008; 38(5): 532 - 540. [Abstract] [Full Text] [PDF]

				M. Bukrinsky and D. Sviridov Human immunodeficiency virus infection and macrophage cholesterol metabolism. J. Leukoc. Biol., November 1, 2006; 80(5): 1044 - 1051. [Abstract] [Full Text] [PDF]

				M. Binder, G. Liebisch, T. Langmann, and G. Schmitz Metabolic Profiling of Glycerophospholipid Synthesis in Fibroblasts Loaded with Free Cholesterol and Modified Low Density Lipoproteins J. Biol. Chem., August 4, 2006; 281(31): 21869 - 21877. [Abstract] [Full Text] [PDF]

				E. E. Griffin, J. C. Ullery, B. E. Cox, and W. G. Jerome Aggregated LDL and lipid dispersions induce lysosomal cholesteryl ester accumulation in macrophage foam cells J. Lipid Res., October 1, 2005; 46(10): 2052 - 2060. [Abstract] [Full Text] [PDF]

				T. Q. Nhan, W. C. Liles, A. Chait, J. T. Fallon, and S. M. Schwartz The p17 Cleaved Form of Caspase-3 Is Present Within Viable Macrophages In Vitro and in Atherosclerotic Plaque Arterioscler Thromb Vasc Biol, July 1, 2003; 23(7): 1276 - 1282. [Abstract] [Full Text] [PDF]

				J. A. Hamilton Nondisposable materials, chronic inflammation, and adjuvant action J. Leukoc. Biol., June 1, 2003; 73(6): 702 - 712. [Abstract] [Full Text] [PDF]

				A. MERTENS and P. HOLVOET Oxidized LDL and HDL: antagonists in atherothrombosis FASEB J, October 1, 2001; 15(12): 2073 - 2084. [Abstract] [Full Text] [PDF]