Phosphocholine as a pattern recognition ligand for CD361

Agnès Boullier; Peter Friedman; Richard Harkewicz; Karsten Hartvigsen; Simone R. Green; Felicidad Almazan; Edward A. Dennis; Daniel Steinberg; Joseph L. Witztum; Oswald Quehenberger

Journal of Lipid Research (May 2005)

Phosphocholine as a pattern recognition ligand for CD361

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

Affiliations

Agnès Boullier: 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
Peter Friedman: 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
Richard Harkewicz: 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
Karsten Hartvigsen: 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
Simone R. Green: 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
Felicidad Almazan: 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
Edward A. Dennis: 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
Daniel Steinberg: 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
Joseph L. Witztum: 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
Oswald Quehenberger: 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

Journal volume & issue: Vol. 46, no. 5
pp. 969 – 976

Abstract

Read online

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.

Published in Journal of Lipid Research

ISSN: 0022-2275 (Print); 1539-7262 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science: Chemistry: Organic chemistry: Biochemistry
Website: https://www.journals.elsevier.com/journal-of-lipid-research

About the journal

Abstract

Keywords