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(Circulation. 2003;108:2498.)
© 2003 American Heart Association, Inc.

Basic Science Reports

Smooth Muscle Cells in Human Atherosclerotic Plaques Express the Fractalkine Receptor CX₃CR1 and Undergo Chemotaxis to the CX₃C Chemokine Fractalkine (CX₃CL1)

Andrew D. Lucas, PhD^*; Christina Bursill, PhD^*; Tomasz J. Guzik, MD, PhD; Jerzy Sadowski, MD, PhD; Keith M. Channon, MD; David R. Greaves, PhD

From the Sir William Dunn School of Pathology, University of Oxford (A.D.L., C.B., D.R.G.), and Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Oxford (C.B., T.J.G., K.M.C.), UK; and the Department of Internal Medicine, Jagiellonian University School of Medicine, J. Dietl Hospital, Kraków, Poland (T.J.G., J.S.).

Correspondence to David R. Greaves, Sir William Dunn School of Pathology, University of Oxford, Oxford, OX1 3RE, UK. E-mail david.greaves{at}path.ox.ac.uk

Received November 14, 2002; de novo received June 11, 2003; revision received August 14, 2003; accepted August 19, 2003.

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.

Key Words: chemokines • atherosclerosis • macrophages • muscle, smooth • remodeling

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