PMID- 23667177 OWN - NLM STAT- MEDLINE DCOM- 20140425 LR - 20211021 IS - 1539-7262 (Electronic) IS - 0022-2275 (Print) IS - 0022-2275 (Linking) VI - 54 IP - 7 DP - 2013 Jul TI - MCP-1 binds to oxidized LDL and is carried by lipoprotein(a) in human plasma. PG - 1877-83 LID - 10.1194/jlr.M036343 [doi] AB - 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. FAU - Wiesner, Philipp AU - Wiesner P AD - Department of Medicine, University of California, San Diego, San Diego, CA, USA. FAU - Tafelmeier, Maria AU - Tafelmeier M FAU - Chittka, Dominik AU - Chittka D FAU - Choi, Soo-Ho AU - Choi SH FAU - Zhang, Li AU - Zhang L FAU - Byun, Young Sup AU - Byun YS FAU - Almazan, Felicidad AU - Almazan F FAU - Yang, Xiaohong AU - Yang X FAU - Iqbal, Navaid AU - Iqbal N FAU - Chowdhury, Punam AU - Chowdhury P FAU - Maisel, Alan AU - Maisel A FAU - Witztum, Joseph L AU - Witztum JL FAU - Handel, Tracy M AU - Handel TM FAU - Tsimikas, Sotirios AU - Tsimikas S FAU - Miller, Yury I AU - Miller YI LA - eng GR - P01 HL088093/HL/NHLBI NIH HHS/United States GR - HL-055798/HL/NHLBI NIH HHS/United States GR - HL-088093/HL/NHLBI NIH HHS/United States GR - AI-037113/AI/NIAID NIH HHS/United States GR - R01 AI037113/AI/NIAID NIH HHS/United States GR - P01 HL055798/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20130510 PL - United States TA - J Lipid Res JT - Journal of lipid research JID - 0376606 RN - 0 (CCL2 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (Lipoprotein(a)) RN - 0 (Lipoproteins, LDL) RN - 0 (Recombinant Proteins) RN - 0 (oxidized low density lipoprotein) SB - IM EIN - J Lipid Res. 2014 Jul;55(7):1549. PMID: 24982241 MH - Animals MH - Binding Sites MH - Chemokine CCL2/blood/*metabolism MH - Humans MH - Lipoprotein(a)/*blood/*metabolism MH - Lipoproteins, LDL/blood/*metabolism MH - Mice MH - Mice, Inbred C57BL MH - Mice, Transgenic MH - Recombinant Proteins/blood/metabolism PMC - PMC3679389 OTO - NOTNLM OT - chemokine (C-C motif) ligand 2 OT - monocyte chemoattractant protein-1 OT - monocyte migration OT - oxidized low density lipoprotein EDAT- 2013/05/15 06:00 MHDA- 2014/04/26 06:00 PMCR- 2014/07/01 CRDT- 2013/05/14 06:00 PHST- 2013/05/14 06:00 [entrez] PHST- 2013/05/15 06:00 [pubmed] PHST- 2014/04/26 06:00 [medline] PHST- 2014/07/01 00:00 [pmc-release] AID - S0022-2275(20)42135-2 [pii] AID - m036343 [pii] AID - 10.1194/jlr.M036343 [doi] PST - ppublish SO - J Lipid Res. 2013 Jul;54(7):1877-83. doi: 10.1194/jlr.M036343. Epub 2013 May 10.