Human vascular smooth muscle cells express receptors for CC chemokines.
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-1alpha (MIP-1alpha) 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-1alpha/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-1alpha on VSMCs was demonstrated by specific binding of biotinylated MIP-1alpha 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.
Hayes
I M
IM
Rhône Poulenc-Rorer, Dagenham Research Centre, Discovery Biology, Essex, UK.
Jordan
N J
NJ
Towers
S
S
Smith
G
G
Paterson
J R
JR
Earnshaw
J J
JJ
Roach
A G
AG
Westwick
J
J
Williams
R J
RJ
D000328:Adult; D000368:Aged; D001161:Arteriosclerosis / Q000378:metabolism; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000378:metabolism; D005260:Female; D006801:Humans; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D018932:Chemokine CCL2; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger; D019707:Receptors, Chemokine