title: Scavenger receptor SR-BI in macrophage lipid metabolism.
abstract: OBJECTIVE
  To investigate the mechanisms by which macrophage scavenger receptor BI (SR-BI) regulates macrophage cholesterol homeostasis and protects against atherosclerosis.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Our results suggest that SR-BI plays a significant role in macrophage cholesterol flux that may partly account for its effects on atherogenesis.
authors.affiliation: Department of Internal Medicine, University of Kentucky, Lexington, KY 40536, USA. ailing.ji@uky.edu
authors.forename: Ailing
authors.initials: A
authors.lastname: Ji
authors.forename: Jason M
authors.initials: JM
authors.lastname: Meyer
authors.forename: Lei
authors.initials: L
authors.lastname: Cai
authors.forename: Akinwunmi
authors.initials: A
authors.lastname: Akinmusire
authors.forename: Maria C
authors.initials: MC
authors.lastname: de Beer
authors.forename: Nancy R
authors.initials: NR
authors.lastname: Webb
authors.forename: Deneys R
authors.initials: DR
authors.lastname: van der Westhuyzen
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism; D019921:Biotinylation; D018955:CD36 Antigens / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism; D017261:Glycosylphosphatidylinositols / Q000378:metabolism; D006706:Homeostasis; D050356:Lipid Metabolism; D008074:Lipoproteins / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000378:metabolism; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018110:Receptors, Lipoprotein / Q000378:metabolism
chemical_list: D018955:CD36 Antigens; D017261:Glycosylphosphatidylinositols; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D018110:Receptors, Lipoprotein; D002784:Cholesterol