PMID- 15136507 OWN - NLM STAT- MEDLINE DCOM- 20041209 LR - 20220310 IS - 1524-4539 (Electronic) IS - 0009-7322 (Linking) VI - 109 IP - 21 DP - 2004 Jun 1 TI - C-reactive protein promotes monocyte chemoattractant protein-1--mediated chemotaxis through upregulating CC chemokine receptor 2 expression in human monocytes. PG - 2566-71 AB - BACKGROUND: Inflammation plays a crucial role in atherosclerosis. An elevated serum C-reactive protein (CRP) level is a strong marker for future atherosclerotic cardiovascular diseases. In addition, recent data suggest that CRP may directly promote atherogenesis. In this study, we investigated whether CRP can directly activate human circulating monocytes. METHODS AND RESULTS: Incubation of THP-1 monocytes with CRP (10 microg/mL) increased CC chemokine receptor 2 (CCR2) expression at both the protein and transcript levels, which in turn enhanced chemotaxis mediated by monocyte chemoattractant protein-1 (MCP-1) up to 2-fold. The CRP-induced upregulation of CCR2 expression involved binding of CRP to the FcgammaR, most notably FcgammaRI, and phospholipase D1 activation. Serum high-sensitivity CRP levels in 52 normocholesterolemic human subjects were positively correlated with CCR2 surface expression on circulating monocytes (r=0.62, P<0.001) and MCP-1-mediated monocyte chemotaxis (r=0.53, P<0.001). CONCLUSIONS: Elevated blood CRP levels may promote accumulation of monocytes in the atherogenic arterial wall by increasing chemotactic activities of monocytes in response to MCP-1. FAU - Han, Ki Hoon AU - Han KH AD - Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea. steadyhan@amc.seoul.kr FAU - Hong, Kyung-Hee AU - Hong KH FAU - Park, Jae-Hyeong AU - Park JH FAU - Ko, Jesang AU - Ko J FAU - Kang, Duk-Hyun AU - Kang DH FAU - Choi, Kee-Joon AU - Choi KJ FAU - Hong, Myeong-Ki AU - Hong MK FAU - Park, Seong-Wook AU - Park SW FAU - Park, Seung-Jung AU - Park SJ LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20040510 PL - United States TA - Circulation JT - Circulation JID - 0147763 RN - 0 (CCL2 protein, human) RN - 0 (CCR2 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (FCGR1A protein, human) RN - 0 (Receptors, CCR2) RN - 0 (Receptors, Chemokine) RN - 0 (Receptors, IgG) RN - 0 (Recombinant Proteins) RN - 9007-41-4 (C-Reactive Protein) RN - 97C5T2UQ7J (Cholesterol) RN - EC 3.1.4.4 (Phospholipase D) RN - EC 3.1.4.4 (phospholipase D1) SB - IM MH - Arteriosclerosis/blood/*physiopathology MH - C-Reactive Protein/*pharmacology MH - Cells, Cultured/drug effects MH - Chemokine CCL2/*physiology MH - Chemotaxis/*drug effects/physiology MH - Cholesterol/blood MH - Enzyme Activation MH - Gene Expression Regulation/drug effects MH - Humans MH - Monocytes/*drug effects/physiology MH - Muscle, Smooth, Vascular/cytology MH - Myocytes, Smooth Muscle/cytology/drug effects MH - Phospholipase D/metabolism MH - Receptors, CCR2 MH - Receptors, Chemokine/*biosynthesis/genetics MH - Receptors, IgG/drug effects/physiology MH - Recombinant Proteins/pharmacology MH - Transcription, Genetic/drug effects MH - Up-Regulation/drug effects EDAT- 2004/05/12 05:00 MHDA- 2004/12/16 09:00 CRDT- 2004/05/12 05:00 PHST- 2004/05/12 05:00 [pubmed] PHST- 2004/12/16 09:00 [medline] PHST- 2004/05/12 05:00 [entrez] AID - 01.CIR.0000131160.94926.6E [pii] AID - 10.1161/01.CIR.0000131160.94926.6E [doi] PST - ppublish SO - Circulation. 2004 Jun 1;109(21):2566-71. doi: 10.1161/01.CIR.0000131160.94926.6E. Epub 2004 May 10.