Macrophage scavenger receptors and foam cell formation.
Scavenger receptors bind and internalize modified low-density lipoprotein (LDL) and high-density lipoprotein (HDL). Because the expression of scavenger receptors is not down-regulated by cholesterol, macrophages (Mphi) expressing scavenger receptors can internalize substantial quantities of cholesteryl ester from oxidized LDL and HDL, leading to foam cell formation. Mphi express several different classes of the growing scavenger receptor family on their cell surface and their relative contribution to Mphi cholesterol physiology and atherogenesis is the subject of intense investigation. We focus on the potential role of two scavenger receptors, macrosialin and SR-BI/II in Mphi cholesterol metabolism. Macrosialin is a predominantly Mphi-specific oxidized LDL-binding protein and an atherogenic diet markedly up-regulates its hepatic expression in atherosclerosis-susceptible and atherosclerosis-resistant mouse strains. The HDL receptor, SR-BI and its splicing variant SR-BII, colocalize with caveolin in caveolae in Mphi. Caveolae are initial acceptor sites for cholesteryl esters and these findings indicate a possible role for caveolae and SR-BI in Mphi-selective lipid uptake and in regulating Mphi cholesterol flux in the vascular wall.
de Villiers
W J
WJ
Department of Internal Medicine, University of Kentucky Medical Center, Lexington 40536-0084, USA. wdevil0@pop.uky.edu
Smart
E J
EJ
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism / Q000502:physiology*; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism / Q000502:physiology*; D018955:CD36 Antigens / Q000378:metabolism / Q000502:physiology*; D005487:Foam Cells / Q000166:cytology*; D006801:Humans; D051907:Lysosomal Membrane Proteins; D008565:Membrane Proteins; D051379:Mice; D011971:Receptors, Immunologic / Q000502:physiology*; D018110:Receptors, Lipoprotein / Q000378:metabolism / Q000502:physiology*; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D012795:Sialoglycoproteins; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D018955:CD36 Antigens; D051907:Lysosomal Membrane Proteins; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D012795:Sialoglycoproteins; C081026:CD68 protein, mouse; D000097382:CD68 Molecule; C074299:SCARB2 protein, human; C454739:Scarb1 protein, mouse