title: Phosphocholine as a pattern recognition ligand for CD36.
abstract: 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.
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, CA 92093-0682, USA.
authors.forename: Agnès
authors.initials: A
authors.lastname: Boullier
authors.forename: Peter
authors.initials: P
authors.lastname: Friedman
authors.forename: Richard
authors.initials: R
authors.lastname: Harkewicz
authors.forename: Karsten
authors.initials: K
authors.lastname: Hartvigsen
authors.forename: Simone R
authors.initials: SR
authors.lastname: Green
authors.forename: Felicidad
authors.initials: F
authors.lastname: Almazan
authors.forename: Edward A
authors.initials: EA
authors.lastname: Dennis
authors.forename: Daniel
authors.initials: D
authors.lastname: Steinberg
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Witztum
authors.forename: Oswald
authors.initials: O
authors.lastname: Quehenberger
mesh_terms: D000818:Animals; D018955:CD36 Antigens / Q000378:metabolism*; D019556:COS Cells; D008024:Ligands; D050356:Lipid Metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D013058:Mass Spectrometry; D010455:Peptides / Q000378:metabolism; D010767:Phosphorylcholine / Q000378:metabolism*
chemical_list: D018955:CD36 Antigens; D008024:Ligands; D008077:Lipoproteins, LDL; D010455:Peptides; D010767:Phosphorylcholine