C-reactive protein (CRP) induces chemokine secretion via CD11b/ICAM-1 interaction in human adherent monocytes.
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.
Montecucco
Fabrizio
F
Department of Cardiology, University Hospital Geneva, 1211 Geneva, Switzerland.
Steffens
Sabine
S
Burger
Fabienne
F
Pelli
Graziano
G
Monaco
Claudia
C
Mach
François
F
D002097:C-Reactive Protein / Q000235:genetics / Q000494:pharmacology*; D039481:CD11b Antigen / Q000502:physiology*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D016923:Cell Death / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D018925:Chemokines / Q000378:metabolism*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology*; D009000:Monocytes / Q000187:drug effects / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D039481:CD11b Antigen; D018925:Chemokines; C509295:ITGAM protein, human; D011994:Recombinant Proteins; D018799:Intercellular Adhesion Molecule-1; D002097:C-Reactive Protein