Beta-chemokine TCA3 binds to and activates rat vascular smooth muscle cells.
The present study compares the activity of TCA3 with other beta-chemokines (macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta, and monocyte chemoattractant protein (MCP)-1) on rat vascular smooth muscle cells. TCA3, MIP-1 alpha, and MCP-1 (but not MIP-1 beta) treatment stimulates chemotaxis of vascular smooth muscle cells. TCA3-mediated chemotactic responses are sensitive to treatment with pertussis toxin, suggesting that G alpha-i proteins are involved in TCA3 signaling of smooth muscle. In addition, TCA3, MIP-1 alpha, and MCP-1 increase vascular smooth muscle cell adhesiveness to type III collagen. In contrast, stimulation with TCA3, but not other beta-chemokines, induces proliferation of vascular smooth muscle cells. TCA3 receptors were identified on rat vascular smooth muscle cells by direct binding of radiolabeled ligand. TCA3 binds to this receptor with high affinity (3 nM). Rat vascular smooth muscle cells display approximately 75,000 binding sites/cell. Competitive inhibition studies indicated that murine MIP-1 alpha, murine MCP-1, and human RANTES are weak partial competitors of TCA3 binding, demonstrating the existence of a unique receptor for TCA3. Murine MIP-1 beta, which fails to stimulate any biologic functions in vascular smooth muscle cells, also does not inhibit TCA3 binding. The combined data demonstrate that TCA3 and other beta-chemokines can modulate vascular smooth muscle cell function.
Luo
Y
Y
Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
D'Amore
P A
PA
Dorf
M E
ME
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects / Q000276:immunology; D016466:CHO Cells; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D054402:Chemokine CCL1; D019742:Chemokines, CC; D002630:Chemotactic Factors / Q000378:metabolism* / Q000494:pharmacology*; D006224:Cricetinae; D016207:Cytokines / Q000378:metabolism* / Q000494:pharmacology*; D007700:Kinetics; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D011485:Protein Binding / Q000187:drug effects / Q000276:immunology; D051381:Rats; D018121:Receptors, Cytokine / Q000032:analysis
C502258:Ccl1 protein, mouse; D054402:Chemokine CCL1; D019742:Chemokines, CC; D002630:Chemotactic Factors; D016207:Cytokines; D018121:Receptors, Cytokine