Fractalkine/CX3CL1 production by human aortic smooth muscle cells impairs monocyte procoagulant and inflammatory responses.
Expression of membrane-bound CX3CL1, a CX(3)C chemokine, can be strongly induced by inflammatory cytokines in primary endothelial cells, mediating capture and tight adhesion of cells, such as monocytes, that carry the CX(3)CR1 receptor. Here, we measured CX3CL1 mRNA and protein induction by human aortic smooth muscle cells (SMCs), another major component of vessel walls, in response to inflammatory stimuli, and analyzed the effect of membrane-bound CX3CL1 on monocyte adhesion, tissue factor (TF) expression, and tumor necrosis factor-alpha (TNF-alpha) released. In human vascular SMCs, CX3CL1 transcripts were induced after 4h of stimulation with a combination of TNF-alpha and interferon-gamma. Cell-associated and shedded CX3CL1 were measured with a specific ELISA, showing that only 30% of the protein was cleaved from the membrane. Expression of CX3CL1 by SMC increased adhesion of monocytic cells, an effect, which was blocked by soluble CX3CL1. Interestingly, monocyte adhesion to CX3CL1-coated plates partially inhibited lipopolysaccharide-induced TF expression and TNF-alpha release. Thus, CX3CL1, in addition to its adhesive/chemotactic functions, directly promotes monocyte antiinflammatory and antiprocoagulant responses. This could have important implications in clinical settings such as atherosclerosis, in which SMCs and monocytic cells are in close proximity.
Ollivier
Véronique
V
INSERM U479, Faculté Xavier Bichat, 75018 Paris, France. ollivier@bichat.inserm.fr
Faure
Sophie
S
Tarantino
Nadine
N
Chollet-Martin
Sylvie
S
Deterre
Philippe
P
Combadière
Christophe
C
de Prost
Dominique
D
D001011:Aorta / Q000166:cytology; D001779:Blood Coagulation Factors / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology; D002450:Cell Communication / Q000276:immunology; D002478:Cells, Cultured; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C / Q000235:genetics / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism / Q000494:pharmacology; D008070:Lipopolysaccharides; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D013925:Thromboplastin / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology
D001779:Blood Coagulation Factors; C515538:CX3CL1 protein, human; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C045071:leukocyte procoagulant activity; D007371:Interferon-gamma; D013925:Thromboplastin