Human vascular smooth muscle cells possess functional CCR5

CC chemokine receptors are important modulators of inflammation. Although C C chemokine receptors have been found predominantly on leukocytes, recent s tudies have suggested that vascular smooth muscle cells respond to CC chemo kines. We now report that human smooth muscle cells express CCR5, a co-rece ptor for human immunodeficiency virus. CCR5 mRNA was detectable by RNA blot hybridization in human aortic and coronary artery smooth muscle cells. The cDNA generated by reverse transcription-polymerase chain reaction from aor tic smooth muscle cells had 100% identity throughout the entire coding regi on with the CCR5 cloned from THP-1 cells. By immunohistochemistry, CCR5 and the CCR5 ligand, macrophage inflammatory protein-1 beta (MIP-1 beta), were detected in smooth muscle cells and macrophages of the atherosclerotic pla que. In smooth muscle cell culture, MIP-1 beta induced a significant increa se in intracellular calcium concentrations, which was blocked by an antibod y to CCR5. In addition, MIP-1 beta caused a calcium-dependent increase in t issue factor activity. Tissue factor is the initiator of coagulation and is thought to play a key role in arterial thrombosis. These data suggest that human arterial smooth muscle cells express functional CCR5 receptors and M IP-1 beta is an agonist for these cells.