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Title

C-reactive protein (CRP) induces chemokine secretion via CD11b/ICAM-1 interaction in human adherent monocytes

Authors
Monaco, Claudia
Published in Journal of Leukocyte Biology. 2008, vol. 84, no. 4, p. 1109-1119
Abstract Several studies support C-reactive protein (CRP) as a systemic cardiovascular risk factor. The recent detection of CRP in arterial intima suggests a dual activity in atherosclerosis as a circulating and tissue mediator on vascular and immune cells. In the present paper, we focused on the inflammatory effects of CRP on human monocytes, which were isolated by Ficoll-Percoll gradients and cultured in adherence to polystyrene, endothelial cell monolayer, or in suspension. Chemokine levels, adhesion molecule, and chemokine receptor expression were detected by ELISA, flow cytometry, and real-time RT-PCR. Migration assays were performed in a Boyden chamber. Stimulation with CRP induced release of CCL2, CCL3, and CCL4 in adherent monocytes through the binding to CD32a, CD32b, and CD64, whereas no effect was observed in suspension culture. This was associated with CRP-induced up-regulation of adhesion molecules membrane-activated complex 1 (Mac-1) and ICAM-1 on adherent monocytes. Blockade of Mac-1/ICAM-1 interaction inhibited the CRP-induced chemokine secretion. In addition, CRP reduced mRNA and surface expression of corresponding chemokine receptors CCR1, CCR2, and CCR5 in adherent monocytes. This effect was a result of chemokine secretion, as coincubation with neutralizing anti-CCL2, anti-CCL3, and anti-CCL4 antibodies reversed the effect of CRP. Accordingly, a reduced migration of CRP-treated monocytes to CCL2 and CCL3 was observed. In conclusion, our data suggest an in vitro model to study CRP activities in adherent and suspension human monocytes. CRP-mediated induction of adhesion molecules and a decrease of chemokine receptors on adherent monocytes might contribute to the retention of monocytes within atherosclerotic lesions and recruitment of other circulating cells.
Keywords Antigens, CD11b/physiologyC-Reactive Protein/genetics/pharmacologyCell Adhesion/drug effects/physiologyCell Death/drug effectsCell Movement/drug effects/physiologyCell Survival/drug effectsChemokines/secretionHumansIntercellular Adhesion Molecule-1/physiologyMonocytes/drug effects/physiologyRecombinant Proteins/pharmacologyReverse Transcriptase Polymerase Chain Reaction
Stable URL http://archive-ouverte.unige.ch/unige:1050
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Other version: http://www.jleukbio.org/cgi/content/full/84/4/1109
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PMID: 18591415
Structures
Research groups Biologie du myocarde (22)
L'athérosclérose et ses complications cliniques (591)
Le rôle du système endocannabinoïde dans l'athérosclérose (882)
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