PMID- 15051635
OWN - NLM
STAT- MEDLINE
DCOM- 20040920
LR  - 20210514
IS  - 1524-4539 (Electronic)
IS  - 0009-7322 (Linking)
VI  - 109
IP  - 16
DP  - 2004 Apr 27
TI  - Conformational rearrangement in C-reactive protein is required for 
      proinflammatory actions on human endothelial cells.
PG  - 2016-22
AB  - BACKGROUND: C-reactive protein (CRP) has been suggested to actively amplify the 
      inflammatory response underlying coronary heart diseases by directly activating 
      endothelial cells. In this study, we investigated whether loss of the cyclic 
      pentameric structure of CRP, resulting in formation of modified or monomeric CRP 
      (mCRP), is a prerequisite for endothelial cell activation. METHODS AND RESULTS: 
      We examined the impact of native CRP and mCRP on the production of monocyte 
      chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8), key regulators of 
      leukocyte recruitment, and on the expression of intercellular adhesion molecule-1 
      (ICAM-1), E-selectin, and vascular adhesion molecule-1 (VCAM-1) in human cultured 
      coronary artery endothelial cells (HCAECs). Incubation with mCRP for 4 hours 
      increased MCP-1 and IL-8 secretion and mRNA levels and expression of ICAM-1, 
      E-selectin, and VCAM-1 protein and mRNA. Significant induction occurred at 1 to 5 
      microg/mL, reached a maximum at 30 microg/mL, and did not require the presence of 
      serum. Native CRP was without detectable effects at 4 hours, whereas it enhanced 
      cytokine release after a 24-hour incubation. An anti-FcgammaRIII (CD16) but not 
      an anti-FcgammaRII (CD32) antibody produced a 14% to 32% reduction of the mCRP 
      effects (P<0.05). mCRP but not CRP evoked phosphorylation of p38 
      mitogen-activated protein kinase, and inhibition of this kinase with SB 203580 
      reversed the effects of mCRP. Furthermore, culture of HCAECs in the presence of 
      SB203580 markedly decreased mCRP-stimulated E-selectin and ICAM-1-dependent 
      adhesion of neutrophils to HCAECs (P<0.001). CONCLUSIONS: Loss of pentameric 
      symmetry in CRP, resulting in formation of mCRP, promotes a proinflammatory HCAEC 
      phenotype through a p38 MAPK-dependent mechanism.
FAU - Khreiss, Tarek
AU  - Khreiss T
AD  - Research Center, Maisonneuve-Rosemont Hospital and Department of Medicine , 
      University of Montreal, Montreal, QC, Canada.
FAU - Jozsef, Levente
AU  - Jozsef L
FAU - Potempa, Lawrence A
AU  - Potempa LA
FAU - Filep, Janos G
AU  - Filep JG
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20040329
PL  - United States
TA  - Circulation
JT  - Circulation
JID - 0147763
RN  - 0 (CRP protein, human)
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Interleukin-8)
RN  - 0 (Receptors, Immunologic)
RN  - 9007-41-4 (C-Reactive Protein)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
CIN - Circulation. 2004 Apr 27;109(16):1914-7. PMID: 15117860
MH  - C-Reactive Protein/*chemistry/pharmacology
MH  - Cell Adhesion
MH  - Cell Adhesion Molecules/biosynthesis
MH  - Chemokine CCL2/metabolism
MH  - Coronary Vessels/cytology
MH  - Endothelium, Vascular/chemistry/cytology/*immunology
MH  - Humans
MH  - Inflammation/immunology
MH  - Interleukin-8/metabolism
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Neutrophils/immunology
MH  - Protein Conformation
MH  - Receptors, Immunologic/analysis
MH  - p38 Mitogen-Activated Protein Kinases
EDAT- 2004/03/31 05:00
MHDA- 2004/09/21 05:00
CRDT- 2004/03/31 05:00
PHST- 2004/03/31 05:00 [pubmed]
PHST- 2004/09/21 05:00 [medline]
PHST- 2004/03/31 05:00 [entrez]
AID - 01.CIR.0000125527.41598.68 [pii]
AID - 10.1161/01.CIR.0000125527.41598.68 [doi]
PST - ppublish
SO  - Circulation. 2004 Apr 27;109(16):2016-22. doi: 
      10.1161/01.CIR.0000125527.41598.68. Epub 2004 Mar 29.