Monocyte chemotactic protein-4: Tissue-specific expression and signaling through CC chemokine receptor-2

Chemokines constitute a family of low-molecular-weight proteins that attract or activate a variety of cell types, including leukocytes, endothelial cells, and fibroblasts, An electronic search of the GenBank Expressed Sequence Tags database uncovered a partial cDNA sequence with homology to the chemokine monocyte chemotactic protein-1 (MCP-1). Isolation of the full-length clone revealed that it encodes the chemokine MCP-4, an eosinophil chemoattractant recently described by Uguccioni et al, [J. Exp Med, 183, 2319-2384], Recombinant MCP-4 was expressed in mammalian cells and purified by heparin-Sepharose chromatography, Sequencing the amino terminus of this protein corroborated the reported sequence of recombinant MCP-4 produced in insect cells, As shown by calcium flux assays, MCP-P activated the cloned G protein-coupled receptor CCR-2, which also recognizee MCP-I and MCP-3, Northern hybridization indicated that MCP-P is constitutively expressed at high levels in the small intestine, colon, and lung, This expression profile is consistent with its role as a chemoattractant for eosinophils, which can be rapidly mobilized to the lung or intestine in response to invading pathogens, In marked contrast to MCP-1, MCP-4 was not induced in cell lines treated with pro-inflammatory stimuli such as lipopolysaccharide or tumor necrosis factor alpha.