MONOCYTE CHEMOTACTIC PROTEIN-4 - TISSUE-SPECIFIC EXPRESSION AND SIGNALING THROUGH CC-CHEMOKINE RECEPTOR-2

Chemokines constitute a family of low-molecular-weight proteins that a ttract or activate a variety of cell types, including leukocytes, endo thelial cells, and fibroblasts, An electronic search of the GenBank Ex pressed Sequence Tags database uncovered a partial cDNA sequence with homology to the chemokine monocyte chemotactic protein-1 (MCP-1). Isol ation of the full-length clone revealed that it encodes the chemokine MCP-4, an eosinophil chemoattractant recently described by Uguccioni e t al, [J. Exp Med, 183, 2319-2384], Recombinant MCP-4 was expressed in mammalian cells and purified by heparin-Sepharose chromatography, Seq uencing the amino terminus of this protein corroborated the reported s equence of recombinant MCP-4 produced in insect cells, As shown by cal cium flux assays, MCP-P activated the cloned G protein-coupled recepto r CCR-2, which also recognizee MCP-I and MCP-3, Northern hybridization indicated that MCP-P is constitutively expressed at high levels in th e small intestine, colon, and lung, This expression profile is consist ent with its role as a chemoattractant for eosinophils, which can be r apidly mobilized to the lung or intestine in response to invading path ogens, In marked contrast to MCP-1, MCP-4 was not induced in cell line s treated with pro-inflammatory stimuli such as lipopolysaccharide or tumor necrosis factor alpha.