C-reactive protein promotes monocyte chemoattractant protein-1--mediated chemotaxis through upregulating CC chemokine receptor 2 expression in human monocytes.
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.


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.
Han
Ki Hoon
KH
Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea. steadyhan@amc.seoul.kr
Hong
Kyung-Hee
KH
Park
Jae-Hyeong
JH
Ko
Jesang
J
Kang
Duk-Hyun
DH
Choi
Kee-Joon
KJ
Hong
Myeong-Ki
MK
Park
Seong-Wook
SW
Park
Seung-Jung
SJ
D001161:Arteriosclerosis / Q000097:blood / Q000503:physiopathology*; D002097:C-Reactive Protein / Q000494:pharmacology*; D002478:Cells, Cultured / Q000187:drug effects; D018932:Chemokine CCL2 / Q000502:physiology*; D002633:Chemotaxis / Q000187:drug effects* / Q000502:physiology; D002784:Cholesterol / Q000097:blood; D004789:Enzyme Activation; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D009000:Monocytes / Q000187:drug effects* / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects; D010739:Phospholipase D / Q000378:metabolism; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000096:biosynthesis* / Q000235:genetics; D017452:Receptors, IgG / Q000187:drug effects / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
C111835:CCL2 protein, human; C515334:CCR2 protein, human; D018932:Chemokine CCL2; C489017:FCGR1A protein, human; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D017452:Receptors, IgG; D011994:Recombinant Proteins; D002097:C-Reactive Protein; D002784:Cholesterol; D010739:Phospholipase D; C106801:phospholipase D1