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Scavenger receptor SR-BI in macrophage lipid metabolism.


ABSTRACT: To investigate the mechanisms by which macrophage scavenger receptor BI (SR-BI) regulates macrophage cholesterol homeostasis and protects against atherosclerosis.The expression and function of SR-BI was investigated in cultured mouse bone marrow-derived macrophages (BMM). SR-BI, the other scavenger receptors SRA and CD36 and the ATP-binding cassette transporters ABCA1 and ABCG1 were each distinctly regulated during BMM differentiation. SR-BI levels increased transiently to significant levels during culture. SR-BI expression in BMM was reversibly down-regulated by lipid loading with modified LDL; SR-BI was shown to be present both on the cell surface as well as intracellularly. BMM exhibited selective HDL CE uptake, however, this was not dependent on SR-BI or another potential candidate glycosylphosphatidylinositol anchored high density lipoprotein binding protein 1 (GPIHBP1). SR-BI played a significant role in facilitating bidirectional cholesterol flux in non lipid-loaded cells. SR-BI expression enhanced both cell cholesterol efflux and cholesterol influx from HDL, but did not lead to altered cellular cholesterol mass. SR-BI-dependent efflux occurred to larger HDL particles but not to smaller HDL(3). Following cholesterol loading, ABCA1 and ABCG1 were up-regulated and served as the major contributors to cholesterol efflux, while SR-BI expression was down-regulated.Our results suggest that SR-BI plays a significant role in macrophage cholesterol flux that may partly account for its effects on atherogenesis.

SUBMITTER: Ji A 

PROVIDER: S-EPMC3139003 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

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Scavenger receptor SR-BI in macrophage lipid metabolism.

Ji Ailing A   Meyer Jason M JM   Cai Lei L   Akinmusire Akinwunmi A   de Beer Maria C MC   Webb Nancy R NR   van der Westhuyzen Deneys R DR  

Atherosclerosis 20110409 1


<h4>Objective</h4>To investigate the mechanisms by which macrophage scavenger receptor BI (SR-BI) regulates macrophage cholesterol homeostasis and protects against atherosclerosis.<h4>Methods and results</h4>The expression and function of SR-BI was investigated in cultured mouse bone marrow-derived macrophages (BMM). SR-BI, the other scavenger receptors SRA and CD36 and the ATP-binding cassette transporters ABCA1 and ABCG1 were each distinctly regulated during BMM differentiation. SR-BI levels i  ...[more]

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