Monocyte chemoattractant protein-3, but not monocyte chemoattractant protein-2, is a functional ligand of the human monocyte chemoattractant protein-1 receptor.

Abstract

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.