Scavenger receptor class B type I as a receptor for oxidized low density lipoprotein.
Scavenger receptor class B type I (SR-BI) has been established as the primary mediator of the selective transfer of lipids from HDL to mammalian cells. In addition to its role in cholesterol metabolism, SR-BI has been shown to bind apoptotic cells and thus could in theory also function as a scavenger receptor. We now show that SR-BI binds oxidized LDL (OxLDL) with high affinity (K(d) of 4.0 +/- 0.5 microg/ml) and mediates internalization and degradation to an extent comparable to that of other scavenger receptors, when normalized to binding activity. The best competitors for OxLDL binding to SR-BI were oxidized lipoproteins, whereas native or acetylated lipoproteins only competed for a small fraction of OxLDL binding. Both the isolated lipids and the isolated protein from OxLDL bound with high affinity to SR-BI and showed partial reciprocal competition. Monoclonal antibody EO6, an antibody against oxidized phospholipids, and 1-palmitoyl-2-(5-oxovaleroyl) phosphatidylcholine (POVPC) both competed effectively with intact OxLDL and with isolated lipids from OxLDL for SR-BI binding.Together, these results demonstrate a potential function of SR-BI, in addition to its role in selective uptake of lipids, to mediate internalization of OxLDL by macrophages and suggest a central role for oxidized phospholipids in this process.
Gillotte-Taylor
K
K
Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Boullier
A
A
Witztum
J L
JL
Steinberg
D
D
Quehenberger
O
O
D000911:Antibodies, Monoclonal / Q000378:metabolism; D001055:Apolipoproteins B / Q000378:metabolism; D017209:Apoptosis; D001667:Binding, Competitive; D018955:CD36 Antigens / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism; D002788:Cholesterol Esters / Q000378:metabolism; D006801:Humans; D007457:Iodine Radioisotopes; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D008565:Membrane Proteins; D010084:Oxidation-Reduction; D010742:Phospholipid Ethers / Q000378:metabolism; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B
C400184:1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphorylcholine; D000911:Antibodies, Monoclonal; D001055:Apolipoproteins B; D018955:CD36 Antigens; D002788:Cholesterol Esters; D007457:Iodine Radioisotopes; D008077:Lipoproteins, LDL; D008565:Membrane Proteins; D010742:Phospholipid Ethers; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C495124:SCARB1 protein, human; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; C099252:oxidized low density lipoprotein; D002784:Cholesterol