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J Lipid Res. 2013 Jul;54(7):1877-83. doi: 10.1194/jlr.M036343. Epub 2013 May 10.

MCP-1 binds to oxidized LDL and is carried by lipoprotein(a) in human plasma.

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1
Department of Medicine, University of California, San Diego, San Diego, CA, USA.

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Abstract

Lipoprotein oxidation plays an important role in pathogenesis of atherosclerosis. Oxidized low density lipoprotein (OxLDL) induces profound inflammatory responses in vascular cells, such as production of monocyte chemoattractant protein-1 (MCP-1) [chemokine (C-C motif) ligand 2], a key chemokine in the initiation and progression of vascular inflammation. Here we demonstrate that OxLDL also binds MCP-1 and that the OxLDL-bound MCP-1 retains its ability to recruit monocytes. A human MCP-1 mutant in which basic amino acids Arg-18 and Lys-19 were replaced with Ala did not bind to OxLDL. The MCP-1 binding to OxLDL was inhibited by the monoclonal antibody E06, which binds oxidized phospholipids (OxPLs) in OxLDL. Because OxPLs are carried by lipoprotein(a) [Lp(a)] in human plasma, we tested to determine whether Lp(a) binds MCP-1. Recombinant wild-type but not mutant MCP-1 added to human plasma bound to Lp(a), and its binding was inhibited by E06. Lp(a) captured from human plasma contained MCP-1 and the Lp(a)-associated endogenous MCP-1 induced monocyte migration. These results demonstrate that OxLDL and Lp(a) bind MCP-1 in vitro and in vivo and that OxPLs are major determinants of the MCP-1 binding. The association of MCP-1 with OxLDL and Lp(a) may play a role in modulating monocyte trafficking during atherogenesis.

KEYWORDS:

chemokine (C-C motif) ligand 2; monocyte chemoattractant protein-1; monocyte migration; oxidized low density lipoprotein

PMID:
23667177
PMCID:
PMC3679389
DOI:
10.1194/jlr.M036343
[Indexed for MEDLINE]
Free PMC Article
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