Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:923-929
© 2001 American Heart Association, Inc.
Vascular Biology |
Linked Chromosome 16q13 Chemokines, Macrophage-Derived Chemokine, Fractalkine, and Thymus- and Activation-Regulated Chemokine, Are Expressed in Human Atherosclerotic Lesions
From the Sir William Dunn School of Pathology (D.R.G., A.D.L., K.L., E.J., C.M.Q., S.G.) University of Oxford, Oxford UK; A.I. Virtanen Institute (T.H., S.Y.-H.), University of Kuopio, Kuopio, Finland; Nuffield Department of Surgery (J.S., F.R.G.), John Radcliffe Hospital, Oxford, UK; and the Division of Cardiovascular Medicine (K.T., J.B., C.S., P.L.W.), Addenbrooke’s Hospital, Cambridge, UK.
Correspondence to David R. Greaves, PhD, Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK. E-mail david.greaves{at}path.ox.ac.uk
Abstract—Chemokines are important mediators of macrophage and T-cell recruitment in a number of inflammatory pathologies, and chemokines expressed in atherosclerotic lesions may play an important role in mononuclear cell recruitment and macrophage differentiation. We have analyzed the expression of the linked chromosome 16q13 genes that encode macrophage-derived chemokine (MDC/CCL22), thymus- and activation-regulated chemokine (TARC/CCL17), and the CX3C chemokine fractalkine (CX3CL1) in primary macrophages and human atherosclerotic lesions by reverse transcription–polymerase chain reaction and immunohistochemistry. We show that macrophage expression of the chemokines MDC, fractalkine, and TARC is upregulated by treatment with the Th2-type cytokines interleukin-4 and interleukin-13. High levels of MDC, TARC, and fractalkine mRNA expression are seen in some, but not all, human arteries with advanced atherosclerotic lesions. Immunohistochemistry shows that MDC, fractalkine, and TARC are expressed by a subset of macrophages within regions of plaques that contain plaque microvessels. We conclude that MDC, fractalkine, and TARC, which are chromosome 16q13 chemokines, could play a role in mononuclear cell recruitment into atherosclerotic lesions and influence the subsequent inflammatory response. Macrophage-expressed chemokines upregulated by interleukin-4 may be useful surrogate markers for the presence of Th2-type immune responses in human atherosclerotic lesions.
Key Words: chemokines • atherosclerosis • macrophages • Th2-type T cells
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