Fractalkine/CX3CL1 production by human aortic smooth muscle cells impairs monocyte procoagulant and inflammatory responses

Expression of membrane-bound CX3CL1, a CX3C 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 fa 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 4 11 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 CX3CL I-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. (C) 2003 Elsevier Science Ltd. All rights reserved.