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)-2and -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 monocyt es, basophils, and T lymphocytes. In this study, we have examined pote ntial interactions of MCP-2 and MCP-3 with the recently cloned MCP-1 r eceptor. MCP-3, but not MCP-2, induced a robust and dose-dependent mob ilization of intracellular calcium in HEK-293 cells that had been stab ly 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 in duced potent inhibition of adenylyl cyclase (concentrations giving 50% inhibition = 48 pM and 67 pM, respectively). MCP-3 bound to HEK-293 c ells stably expressing the MCP-1 receptor, but with approximately 35-f old lower affinity than MCP-1. MCP-1 desensitized transfected HEK-293 cells expressing the MCP-1 receptor to activation by MCP-3 in the calc ium mobilization assay, but MCP-3 did not effectively desensitize thes e cells to MCP-1. We conclude that MCP-3, but not MCP-2, is a function al ligand for the MCP-1 receptor.