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C‐reactive protein (CRP) induces chemokine secretion via CD11b/ICAM‐1 interaction in human adherent monocytes
Author(s) -
Montecucco Fabrizio,
Steffens Sabine,
Burger Fabienne,
Pelli Graziano,
Monaco Claudia,
Mach François
Publication year - 2008
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0208123
Subject(s) - chemokine , biology , chemokine receptor , ccl3 , immunology , monocyte , cd64 , ccr1 , cell adhesion molecule , microbiology and biotechnology , ccl2 , flow cytometry , inflammation
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.