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Monocyte chemotactic protein‐4: tissue‐specific expression and signaling through CC chemokine receptor‐2
Author(s) -
Godiska Ronald,
Chantry David,
Raport Carol J.,
Schweickart Vicki L.,
Le Trong Hai,
Gray Patrick W.
Publication year - 1997
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.61.3.353
Subject(s) - biology , chemokine , microbiology and biotechnology , monocyte , chemotaxis , ccl7 , cxcl2 , eotaxin , ccl17 , chemokine receptor , receptor , immunology , biochemistry
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, 2379–2384]. 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‐4 activated the cloned G protein‐coupled receptor CCR‐2, which also recognizes MCP‐1 and MCP‐3. Northern hybridization indicated that MCP‐4 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 α. J. Leukoc. Biol . 61: 353–360; 1997.