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, 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 alpha.
Godiska
R
R
ICOS Corporation, Bothell, Washington 98021, USA.
Chantry
D
D
Raport
C J
CJ
Schweickart
V L
VL
Trong
H L
HL
Gray
P W
PW
D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D054410:Chemokine CCL7; D006224:Cricetinae; D016207:Cytokines; D018076:DNA, Complementary / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008969:Molecular Sequence Data; D018945:Monocyte Chemoattractant Proteins / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D014162:Transfection
C099677:CCL13 protein, human; C515450:CCL7 protein, human; C515334:CCR2 protein, human; D054410:Chemokine CCL7; D016207:Cytokines; D018076:DNA, Complementary; D018945:Monocyte Chemoattractant Proteins; D012333:RNA, Messenger; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D002118:Calcium