Published Online
on October 27, 2003

A more recent version of this article appeared on November 18, 2003

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Submitted on November 14, 2002
Revised on August 14, 2003
Accepted on August 19, 2003

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, and 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.).

^* To whom correspondence should be addressed. E-mail: david.greaves{at}path.ox.ac.uk.

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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