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Papers In Press, published online ahead of print May 1, 2005
J. Lipid Res., doi:10.1194/jlr.M400496-JLR200

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Journal of Lipid Research, Vol. 46, 969-976, May 2005
Copyright © 2005 by American Society for Biochemistry and Molecular Biology

Phosphocholine as a pattern recognition ligand for CD36^1,

Agnès Boullier^2,*, Peter Friedman^2,, Richard Harkewicz, Karsten Hartvigsen^*, Simone R. Green^*, Felicidad Almazan^*, Edward A. Dennis, Daniel Steinberg^*, Joseph L. Witztum^* and Oswald Quehenberger^3,*

^* Department of Medicine, University of California San Diego, La Jolla, CA 92093-0682
Departments of Chemistry, Biochemistry, and Pharmacology, University of California San Diego, La Jolla, CA 92093-0682

¹ Trudy Forte served as Guest Editor for this manuscript.

The online version of this article (available at http://www.jlr.org) contains an additional table and two figures.

Published, JLR Papers in Press, February 1, 2005. DOI 10.1194/jlr.M400496-JLR200

² A Boullier and P. Friedman contributed equally to this work.

³ To whom correspondence should be addressed. e-mail: oquehenberger{at}ucsd.edu

We have previously shown that CD36 recognizes oxidation products of phospholipids on oxidized LDL (OxLDL) such as 1-palmitoyl-2-(5'-oxovaleroyl)-sn-glycero-3-phosphocholine (POVPC). The current study was designed to examine whether the phosphocholine (PC) headgroup in POVPC constitutes an obligatory binding target for CD36. To examine the contribution of PC in the binding of POVPC to CD36, we used well-defined synthetic oxidized phospholipids (OxPLs) cross-linked to BSA or to a hexapeptide. The OxPL adducts were then tested for their ability to bind to CD36-transfected cells and for their ability to inhibit OxLDL binding to CD36. Both POVPC-BSA and POVPC-peptide adducts were high-affinity ligands for CD36 and potent inhibitors of OxLDL binding. Enzymatic removal of the entire PC moiety of the POVPC-peptide, or of the choline headgroup alone, as well as substitution of the choline headgroup by ethanolamine abrogated the inhibitory activity of POVPC. Interestingly, PC by itself or cross-linked to BSA did not show any intrinsic competition activity.

In conclusion, our data demonstrate that the PC headgroup of OxPL alone is sufficient for binding to CD36, but only if presented in the correct conformation as in OxPL of OxLDL or as in POVPC-peptide adducts.

Abbreviations: Ac-TGTKGY, Ac-threonine-glycine-threonine-lysine-glycine-tyrosine; apoE, apolipoprotein E; KLH, keyhole limpet hemocyanin; OxLDL, oxidized low density lipoprotein; OxPL, oxidized phospholipid; PAMP, pathogen-associated molecular pattern; PC, phosphocholine; PLC, phospholipase C; PLD, phospholipase D; POVG, 1-palmitoyl-2-(5'-oxovaleroyl)-glycerol; POVPA, 1-palmitoyl-2-(5'-oxovaleroyl)-sn-glycero-3-phosphatidic acid; POVPC, 1-palmitoyl-2-(5'-oxovaleroyl)-sn-glycero-3-phosphocholine; POVPE, 1-palmitoyl-2-(5'-oxovaleroyl)-sn-glycero-3-phosphoethanolamine

Supplementary key words scavenger receptor • oxidized phospholipids • atherosclerosis

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