Human Vascular Smooth Muscle Cells Express Receptors for CC Chemokines

From Rhône Poulenc–Rorer, Dagenham Research Centre, Discovery Biology, Essex (I.M.H., S.T., J.R.P., A.G.R., R.J.W.); the University of Bath, Department of Pharmacology, (N.J.J., G.S., J.W.); and Gloucestershire Royal Hospital (J.J.E.), UK.

Correspondence to Dr Ian Hayes, Discovery Biology, Rhône Poulenc–Rorer, Dagenham Research Centre, Rainham Road South, Dagenham, Essex, RM10 7XS, UK.

Abstract—Arteriosclerotic lesions are characterized by the accumulation of T lymphocytes and monocytes and the proliferation of intimal smooth muscle cells. Expression of the chemokine monocyte chemoattractant protein-1 (MCP-1) has been observed in arteriosclerotic plaques and has been proposed to mediate the transendothelial migration of mononuclear cells. More recently, MCP-1 has been proposed to affect the proliferation and migration of vascular smooth muscle cells (VSMCs). We have used reverse transcription–polymerase chain reaction (RT-PCR) to investigate chemokine mRNA expression in human arteriosclerotic lesions obtained from surgical biopsy of diseased vascular tissue and show, in addition to MCP-1, expression of the chemokine macrophage inflammatory protein-1 (MIP-1) at higher levels than in "normal" aortic tissue. We have also used RT-PCR to characterize the expression of known chemokine receptors by primary human VSMCs. Messenger RNA for the MIP-1/RANTES receptor, CCR-1, and the MCP-1/MCP-3 receptor, CCR-2, was expressed by unstimulated VSMCs grown under serum-free culture conditions for 24 hours. The receptors CCR-3, CCR-4, CCR-5, CXCR-1, and CXCR-2 were not expressed by VSMCs. The presence of functionally coupled receptors for MIP-1 on VSMCs was demonstrated by specific binding of biotinylated MIP-1 and increases in intracellular Ca²⁺ levels after exposure to this chemokine. Taken together, these results suggest that chemokines are likely to be involved in arteriosclerosis and may play a role in modulating the function of VSMCs in vivo.

Key Words: chemokines • receptors • humans • vascular smooth muscle cells • arteriosclerosis

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