Published online before print March 29, 2004, doi: 10.1161/01.CIR.0000125527.41598.68
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(Circulation. 2004;109:2016-2022.)
© 2004 American Heart Association, Inc.
Basic Science Reports |
Conformational Rearrangement in C-Reactive Protein Is Required for Proinflammatory Actions on Human Endothelial Cells
From the Research Center, Maisonneuve-Rosemont Hospital and Department of Medicine (T.K., L.J., J.G.F.), University of Montreal, Montreal, QC, Canada, and Immtech International, Inc (L.A.P.), Vernon Hills, Ill.
Correspondence to János G. Filep, MD, Research Center, Maisonneuve-Rosemont Hospital, 5415 boulevard de l’Assomption, Montreal, Quebec, Canada H1T 2M4. E-mail janos.g.filep{at}umontreal.ca
Received July 10, 2003; de novo received October 14, 2003; revision received January 5, 2004; accepted January 12, 2004.
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 µg/mL, reached a maximum at 30 µg/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-Fc
RIII (CD16) but not an anti-FcRII (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.
Key Words: proteins • cell adhesion molecules • signal transduction • endothelium • inflammation
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|
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|
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|
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