Conformational Rearrangement in C-Reactive Protein Is Required for Proinflammatory Actions on Human Endothelial Cells
| Autor: | Lawrence A. Potempa, János G. Filep, Levente Jozsef, Tarek Khreiss |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Endothelium
Neutrophils Protein Conformation Inflammation Biology p38 Mitogen-Activated Protein Kinases Proinflammatory cytokine Physiology (medical) Cell Adhesion medicine Humans Secretion Receptors Immunologic Chemokine CCL2 Cell adhesion molecule Monocyte Interleukin-8 Coronary Vessels Cell biology Endothelial stem cell C-Reactive Protein medicine.anatomical_structure Endothelium Vascular Mitogen-Activated Protein Kinases medicine.symptom Signal transduction Cardiology and Cardiovascular Medicine Cell Adhesion Molecules |
| Zdroj: | Circulation. 109:2016-2022 |
| ISSN: | 1524-4539 0009-7322 |
| DOI: | 10.1161/01.cir.0000125527.41598.68 |
| Popis: | 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-FcγRIII (CD16) but not an anti-FcγRII (CD32) antibody produced a 14% to 32% reduction of the mCRP effects (PPConclusions—Loss of pentameric symmetry in CRP, resulting in formation of mCRP, promotes a proinflammatory HCAEC phenotype through a p38 MAPK–dependent mechanism. |
| Databáze: | OpenAIRE |
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