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J. Biol. Chem., Vol. 277, Issue 41, 38503-38516, October 11, 2002
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From the The macrophage scavenger receptor CD36 plays an
important role in the uptake of oxidized forms of low density
lipoprotein (LDL) and contributes to lesion development in murine
models of atherosclerosis. However, the structural basis of CD36
lipoprotein ligand recognition is unknown. We now identify a novel
class of oxidized phospholipids that serve as high affinity ligands for CD36 and mediate recognition of oxidized forms of LDL by CD36 on
macrophages. Small unilamellar vesicles of homogeneous
phosphatidylcholine (PC) molecular species were oxidized by the
myeloperoxidase
(MPO)-H2O2-NO
Identification of a Novel Family of Oxidized Phospholipids That
Serve as Ligands for the Macrophage Scavenger Receptor CD36*
,¶,
**,,**,,,§§
Department of Cell Biology and
Department of Cardiovascular Medicine, Cleveland Clinic
Foundation, Cleveland, Ohio 44195, the § Department of
Chemistry, Case Western Reserve University, Cleveland, Ohio 44106, the Department of Chemistry, Cleveland
State University, Cleveland, Ohio 44115, and the Center for
Cardiovascular Diagnostics and Prevention, Preventive Cardiology
Section, Cleveland Clinic Foundation, Cleveland, Ohio 44195
-hydroxy(or
oxo)-
,
-unsaturated carbonyl (oxPCCD36). LC/ESI/MS/MS
studies demonstrate that oxPCCD36 are formed during LDL
oxidation by multiple distinct pathways. Formation of this novel class
of oxidized PC species contributes to CD36-mediated recognition of LDL
oxidized by MPO and other biologically relevant mechanisms. The present
results offer structural insights into the molecular patterns
recognized by the scavenger receptor CD36 and provide a platform for
the development of potential therapeutic inhibitory agents.
*
This work was supported in part by National Institutes of
Health Grants HL62526, HL70621, HL61878 (to S. L. H.), GM21249 (to R. G. S.), and HL53315 (to H. F. H. and R. G. S.), and a
Scientist Development grant from the American Heart Association (to
E. A. P.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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