Monocyte chemoattractant protein-3, but not monocyte chemoattractant protein-2, is a functional ligand of the human monocyte chemoattractant protein-1 receptor.
Monocyte chemoattractant protein (MCP)-2 and -3 are recently identified members of the Cys-Cys chemokine family and are highly homologous to MCP-1. MCP-1, MCP-2, and MCP-3 are potent chemoattractants for monocytes, basophils, and T lymphocytes. In this study, we have examined potential interactions of MCP-2 and MCP-3 with the recently cloned MCP-1 receptor. MCP-3, but not MCP-2, induced a robust and dose-dependent mobilization of intracellular calcium in HEK-293 cells that had been stably transfected with the MCP-1 receptor. The kinetics of these calcium transients were similar to those elicited by MCP-1. MCP-1 and MCP-3 induced potent inhibition of adenylyl cyclase (concentrations giving 50% inhibition = 48 pM and 67 pM, respectively). MCP-3 bound to HEK-293 cells stably expressing the MCP-1 receptor, but with approximately 35-fold lower affinity than MCP-1. MCP-1 desensitized transfected HEK-293 cells expressing the MCP-1 receptor to activation by MCP-3 in the calcium mobilization assay, but MCP-3 did not effectively desensitize these cells to MCP-1. We conclude that MCP-3, but not MCP-2, is a functional ligand for the MCP-1 receptor.
Franci
C
C
Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94110, USA.
Wong
L M
LM
Van Damme
J
J
Proost
P
P
Charo
I F
IF
D000067956:Adenylyl Cyclase Inhibitors; D000595:Amino Acid Sequence; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D018932:Chemokine CCL2; D054410:Chemokine CCL7; D054412:Chemokine CCL8; D002630:Chemotactic Factors / Q000235:genetics / Q000378:metabolism*; D003001:Cloning, Molecular; D017124:Conserved Sequence; D016207:Cytokines; D006801:Humans; D008024:Ligands; D008969:Molecular Sequence Data; D018945:Monocyte Chemoattractant Proteins; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D014162:Transfection
D000067956:Adenylyl Cyclase Inhibitors; C515450:CCL7 protein, human; C515453:CCL8 protein, human; C515334:CCR2 protein, human; D018932:Chemokine CCL2; D054410:Chemokine CCL7; D054412:Chemokine CCL8; D002630:Chemotactic Factors; D016207:Cytokines; D008024:Ligands; D018945:Monocyte Chemoattractant Proteins; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D002118:Calcium