J. Lipid Res.
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Journal of Lipid Research, Vol. 42, 1474-1482, September 2001
Copyright © 2001 by Lipid Research, Inc.


Original Article

Scavenger receptor class B type I as a receptor for oxidized low density lipoprotein

Kristin Gillotte-Taylora, Agnès Boulliera, Joseph L. Witztuma, Daniel Steinberga, and Oswald Quehenbergera
a Department of Medicine, University of California, San Diego, La Jolla, CA 92093

Correspondence to: Oswald Quehenberger, at the University of California, San Diego, Department of Medicine, 9500 Gilman Drive, La Jolla, CA 92093-0682., oquehenberger{at}ucsd.edu (E-mail)

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 (Kd of 4.0 ± 0.5 µg/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., A. Boullier, J. L. Witztum, D. Steinberg, and O. Quehenberger. Scavenger receptor class B type I as a receptor for oxidized low density lipoprotein. J. Lipid Res. 2001. 42: 1474;–1482.

Supplementary key words: oxidized LDL, SR-BI, oxidized phospholipid, scavenger receptor


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