Conformational rearrangement in C-reactive protein is required for proinflammatory actions on human endothelial cells

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 monomeri...

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Bibliographic Details
Published in:Circulation (New York, N.Y.) N.Y.), 2004-04, Vol.109 (16), p.2016-2022
Main Authors: KHREISS, Tarek, JOZSEF, Levente, POTEMPA, Lawrence A, FILEP, Janos G
Format: Article
Language:English
Subjects:
Biological and medical sciences
Blood and lymphatic vessels
C-Reactive Protein - chemistry
C-Reactive Protein - pharmacology
Cardiology. Vascular system
Cell Adhesion
Cell Adhesion Molecules - biosynthesis
Chemokine CCL2 - metabolism
Coronary Vessels - cytology
Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous
Endothelium, Vascular - chemistry
Endothelium, Vascular - cytology
Endothelium, Vascular - immunology
Humans
Inflammation - immunology
Interleukin-8 - metabolism
Medical sciences
Mitogen-Activated Protein Kinases - metabolism
Neutrophils - immunology
p38 Mitogen-Activated Protein Kinases
Protein Conformation
Receptors, Immunologic - analysis
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Summary: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. 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
ISSN:0009-7322
1524-4539
DOI:10.1161/01.cir.0000125527.41598.68