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Journal of Lipid Research, Vol. 47, 2408-2421, November 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology

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^1,*

^* University Hospital Hamburg Eppendorf, 20246 Hamburg, Germany
Harvard Medical School, Massachusetts General Hospital, Boston, MA 02114

Published, JLR Papers in Press, August 22, 2006.

¹ To whom correspondence should be addressed. e-mail: rinninger{at}uke.uni-hamburg.de

Scavenger receptor class B type I (SR-BI) mediates the selective uptake of HDL cholesteryl esters (CEs) and facilitates the 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. Macrophages and HDL originated from wild-type (WT) or SR-BI knockout (KO; homozygous) mice. For uptake, macrophages were 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]cholesteryl oleyl ether – ¹²⁵I-tyramine cellobiose) was similar in WT and SR-BI KO macrophages. Radiolabeled SR-BI KO-HDL yielded a lower rate of selective uptake compared with WT-HDL in WT and SR-BI KO macrophages. Cholesterol efflux was similar in WT and SR-BI KO cells using HDL as acceptor. SR-BI KO-HDL more efficiently promoted cholesterol removal compared with WT-HDL from both types of macrophages. Macrophages selectively take up HDL CE independently of SR-BI. Additionally, in macrophages, there is substantial cholesterol efflux that 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 with WT-HDL, whereas SR-BI KO-HDL more efficiently promotes cholesterol efflux.

Supplementary key words high density lipoprotein • scavenger receptor class B type I • reverse cholesterol transport

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