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) All Versions of this Article: M200464-JLR200v1 44/6/1156    most recent 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 Liu, S. M. Articles by Kritharides, L. Search for Related Content PubMed PubMed Citation Articles by Liu, S. M. Articles by Kritharides, L. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol. 44, 1156-1166, June 2003
Copyright © 2003 by Lipid Research, Inc.

Cyclodextrins differentially mobilize free and esterified cholesterol from primary human foam cell macrophages

Sue M. Liu^1,*, Anne Cogny^1,*, Maaike Kockx^1,, Roger T. Dean, Katharina Gaus, Wendy Jessup and Leonard Kritharides^2,*,,**

^* Heart Research Institute, Camperdown, Sydney New South Wales, Australia
Macrophage Biology Group, Centre for Thrombosis and Vascular Research, University of New South Wales, Australia
University of Canberra, ACT, Australia
^** Department of Cardiology, Concord Hospital, University of Sydney, Australia

² To whom correspondence should be addressed. e-mail: l.kritharides{at}unsw.edu.au

Human monocyte-derived foam cell macrophages (HMFCs) are resistant to cholesterol efflux mediated by physiological acceptors. The role of the plasma membrane in regulating depletion of free cholesterol (FC) and of cholesteryl ester (CE) was investigated using cyclodextrins (CDs). HMFCs were incubated in media containing CDs (1.0 mg/ml, 0.7 mM) with low [hydroxypropyl-ß-CD (HP-CD)] or high [trimethyl-ß-CD (TM-CD)] affinity for cholesterol in the presence or absence of phospholipid vesicles (PLVs). Low-affinity HP-CD caused minimal cholesterol efflux on its own, but HP-CD+ PLV depleted cell FC and CE to 54.5 ± 6.7% of control by 24 h. TM-CD depleted FC at least as well as HP-CD+PLV but without depleting CE, even when combined with PLV. This was not explained by acceptor saturation, instability of PLV vesicles, de novo cholesterol synthesis, kinetically distinct cholesterol pools, or inhibition of CE hydrolysis. TM-CD did, however, deplete CE when lower concentrations of TM-CD were combined with PLV and when acetyl-CoA cholesteryl acyltransferase was inhibited. TM-CD caused much greater depletion of plasma membrane cholesterol than HP-CD without depleting plasma membrane sphingomyelin.

It is concluded that differential depletion of plasma membrane cholesterol pools regulates cholesterol efflux and CE clearance in human macrophages.

Abbreviations: CD, cyclodextrin; CE, cholesteryl ester; FC, free cholesterol; HMFC, human monocyte-derived foam cell macrophage; HP-CD, hydroxypropyl-ß-CD; LPC, lysophosphatidylcholine; PC, phosphatidylcholine; PLV, phospholipid vesicles; SPM, sphingomyelin; TM-CD, trimethyl-ß-CD

Supplementary key words cholesterol efflux • high density lipoprotein • atherosclerosis • plasma membrane

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

This article has been cited by other articles:

				K. Gaus, M. Rodriguez, K. R. Ruberu, I. Gelissen, T. M. Sloane, L. Kritharides, and W. Jessup Domain-specific lipid distribution in macrophage plasma membranes J. Lipid Res., July 1, 2005; 46(7): 1526 - 1538. [Abstract] [Full Text] [PDF]

				E. N. Glaros, W. S. Kim, C. M. Quinn, J. Wong, I. Gelissen, W. Jessup, and B. Garner Glycosphingolipid Accumulation Inhibits Cholesterol Efflux via the ABCA1/Apolipoprotein A-I Pathway: 1-PHENYL-2-DECANOYLAMINO-3-MORPHOLINO-1-PROPANOL IS A NOVEL CHOLESTEROL EFFLUX ACCELERATOR J. Biol. Chem., July 1, 2005; 280(26): 24515 - 24523. [Abstract] [Full Text] [PDF]