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Originally published online as doi:10.1189/jlb.0208123 on June 30, 2008

Published online before print June 30, 2008
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(Journal of Leukocyte Biology. 2008;84:1109-1119.)
© 2008 by Society for Leukocyte Biology

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

Fabrizio Montecucco*,1, Sabine Steffens*,1, Fabienne Burger*, Graziano Pelli*, Claudia Monaco{dagger} and François Mach*,2

* Division of Cardiology, University Hospital Geneva, Faculty of Medicine, Foundation for Medical Research, Geneva, Switzerland; and
{dagger} Kennedy Institute of Rheumatology, Imperial College London, United Kingdom

2 Correspondence: Cardiology Division, University Hospital Geneva, Faculty of Medicine, 64 Avenue Roseraie, 1211 Geneva, Switzerland. E-mail: francois.mach{at}medecine.unige.ch

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.

Key Words: atherosclerosis • inflammation • adhesion molecules • leukocytes




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F. Montecucco, F. Burger, G. Pelli, N. K. Poku, C. Berlier, S. Steffens, and F. Mach
Statins inhibit C-reactive protein-induced chemokine secretion, ICAM-1 upregulation and chemotaxis in adherent human monocytes
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