J. Lipid Res.  Neurobiology of Lipids (ISSN1683-5506)
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A more recent version of this article appeared on November 1, 2006

Papers In Press, published online ahead of print August 22, 2006
J. Lipid Res., doi:10.1194/jlr.M600136-JLR200
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Submitted on March 21, 2006
Revised on August 2, 2006
Accepted on August 22, 2006

Selective uptake of HDL cholesteryl esters and cholesterol efflux from mouse peritoneal macrophages independent of SR-BI

May Brundert, Joerg Heeren, Mukaddes Bahar-Bayansar, Anne Ewert, Kathryn J. Moore, and Franz Rinninger

Department of Medicine, Hospital Eppendorf, Hamburg, Hamburg 20246

Corresponding Author: Rinninger{at}uke.uni-hamburg.de

Objective - Scavenger receptor class B type I (SR-BI) mediates selective uptake of HDL cholesteryl esters (CE) and facilitates efflux of unesterified cholesterol. SR-BI expression in macrophages presumably plays a role in atherosclerosis. The role of SR-BI for selective CE uptake and cholesterol efflux in macrophages was explored. Methods and Results - Macrophages and HDL originated from wildtype (WT) or SR-BI Knockout (KO, homozygous) mice. For uptake, macrophages incubated in medium containing 125I-/[3H]-labeled HDL. For lipid removal, [3H]cholesterol efflux was analyzed using HDL as acceptor. Selective uptake of HDL CE ([3H]CEt – 125I-TC) was similar in WT and in SR-BI KO macrophages. Radiolabeled SR-BI KO-HDL yielded a lower rate of selective uptake compared to WT-HDL in WT and in SR-BI KO macrophages. Cholesterol efflux was similar in WT and in SR-BI KO cells using HDL as acceptor. SR-BI KO-HDL more efficiently promoted cholesterol removal compared to WT-HDL from both types of macrophages. Conclusions - Macrophages selectively take up HDL CE independently from SR-BI. Besides, in macrophages there is substantial cholesterol efflux which is not mediated by SR-BI. Therefore SR-BI-independent mechanisms mediate selective CE uptake and cholesterol removal. SR-BI KO-HDL is an inferior donor for selective CE uptake compared to WT-HDL whereas SR-BI KO-HDL more efficiently promotes cholesterol efflux.


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L. Yvan-Charvet, T. A. Pagler, N. Wang, T. Senokuchi, M. Brundert, H. Li, F. Rinninger, and A. R. Tall
SR-BI inhibits ABCG1-stimulated net cholesterol efflux from cells to plasma HDL
J. Lipid Res., January 1, 2008; 49(1): 107 - 114.
[Abstract] [Full Text] [PDF]




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