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

ScavengerreceptorclassBtypeI(SR-BI)mediates the selective uptake of HDL cholesteryl esters (CEs) and facilitates the efflux of unesterified cholesterol. SR-BI ex- pression in macrophages presumably plays a role in athero- sclerosis. The role of SR-BI for selective CE uptake and cholesterol efflux in macrophages was explored. Macro- phages and HDL originated from wild-type (WT) or SR-BI knockout(KO;homozygous)mice.Foruptake,macrophages wereincubatedinmediumcontaining 125 I-/ 3 H-labeledHDL. For lipid removal, ( 3 H)cholesterol efflux was analyzed using HDL as acceptor. Selective uptake of HDL CE (( 3 H)choles- teryloleylether2 125 I-tyraminecellobiose)wassimilarinWT 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 accep- tor. SR-BI KO-HDL more efficiently promoted cholesterol removal compared with WT-HDL from both types of macro- phages. Macrophages selectively take up HDL CE inde- pendently of SR-BI. Additionally, in macrophages, there is substantial cholesterol efflux that is not mediated by SR-BI. Therefore, SR-BI-independent mechanisms me- diate selective CE uptake and cholesterol removal. SR-BI KO-HDL is an inferior donor for selective CE uptake com- pared with WT-HDL, whereas SR-BI KO-HDL more effi- ciently promotes cholesterol efflux.—Brundert, M., J. Heeren, M. Bahar-Bayansar, A. Ewert, K. J. Moore, and F. Rinninger. Selective uptake of HDL cholesteryl esters and cholesterol efflux from mouse peritoneal macrophages independent of SR-BI. J. Lipid Res. 2006. 47: 2408-2421.