Smooth muscle cells in human atherosclerotic plaques express the fractalkine receptor CX3CR1 and undergo chemotaxis to the CX3C chemokine fractalkine (CX3CL1).

Journal article

BACKGROUND: Chemokines are important mediators of inflammatory cell recruitment that play a significant role in atherosclerosis. Fractalkine (CX3CL1) is an unusual membrane-bound chemokine that mediates chemotaxis through the CX3CR1 receptor. Recently, functional polymorphisms in the human CX3CR1 gene have been described that are associated with coronary artery disease. METHODS AND RESULTS: We investigated the expression of the CX3C chemokine fractalkine and its receptor CX3CR1 in human coronary artery plaques by immunocytometry. We show that a subset of mononuclear cells expresses high levels of fractalkine in human coronary atherosclerotic plaques and that smooth muscle cells within the neointima express the fractalkine receptor CX3CR1. There is a positive correlation between the number of fractalkine-expressing cells and the number of CX3CR1-positive cells in human atherosclerotic plaques (r=0.70, n=15 plaques). Furthermore, we demonstrate that cultured vascular smooth muscle cells express the CX3CR1 receptor and undergo chemotaxis to fractalkine that can be inhibited by G protein inactivation by pertussis toxin. CONCLUSIONS: These results suggest that in human atherosclerosis, fractalkine, rather than mediating inflammatory cell recruitment, can act as a mediator of smooth muscle cell migration.

Authors: Lucas, A; Bursill, C; Guzik, T; Sadowski, J; Channon, K

• Publication status: Published
• Journal: Circulation
• Volume: 108
• Issue: 20
• Pages: 2498-2504
• Publication date: 2003-11-01
• DOI: 10.1161/01.cir.0000097119.57756.ef
• EISSN: 1524-4539
• ISSN: 0009-7322
• Language: English
• Keywords: Antigens, CD14; Female; Cells, Cultured; Muscle, Smooth, Vascular; Cell Count; Antigens, Differentiation, Myelomonocytic; Middle Aged; Male; Leukocytes, Mononuclear; Membrane Proteins; Cell Movement; Antigens, CD3; Chemotaxis; Adult; Pertussis Toxin; Antigens, CD; Humans; Arteriosclerosis; Chemokine CX3CL1; Chemokines, CX3C