Molecular cloning and characterization of a novel CXC chemokine macrophageinflammatory protein-2 gamma chemoattractant for human neutrophils and dendritic cells
Xt. Cao et al., Molecular cloning and characterization of a novel CXC chemokine macrophageinflammatory protein-2 gamma chemoattractant for human neutrophils and dendritic cells, J IMMUNOL, 165(5), 2000, pp. 2588-2595
Chemokines play important roles in leukocyte trafficking as well as functio
n regulation. In this study, we described the identification and characteri
zation of a novel CXC chemokine from a human dendritic cell (DC) cDNA libra
ry, the full-length cDNA of which contains an open reading frame encoding 1
11 aa with a putative signal peptide of 34 aa, This CXC chemokine shares gr
eatest homology with macrophage inflammatory protein (MIP)-2 alpha beta, he
nce is designated as MIP-2 gamma, mouse MIP-2 gamma was identified by elect
rocloning and is highly homologous to human MIP-2 gamma, Northern blotting
revealed that MIP-2 gamma was constitutively and widely expressed in most n
ormal tissues with the greatest expression in kidney, but undetectable in m
ost tumor cell lines except THP-1 cells. In situ hybridization analysis dem
onstrated that MIP-2 gamma was mainly expressed by the epithelium of tubule
s in the kidney and hepatocytes in the liver, Although no detectable expres
sion was observed in freshly isolated or PMA-treated monocytes, RT-PCR anal
ysis revealed MIP-2 gamma expression by monocyte-derived DC. Recombinant MI
P-2 gamma front 293 cells is about 9.5 kDa in size and specifically detecta
ble by its polyclonal Ab developed by the immunization with its 6His-tagged
fusion protein. The eukaryotically expressed MIP-2 gamma is a potent chemo
attractant for neutrophils, and weaker for DC, but inactive to monocytes, N
K cells, and T and B lymphocytes. Receptor binding assays showed that MIP-2
gamma does not bind to CXCR2, This implies that DC might contribute to the
innate immunity through the production of neutrophil-attracting chemokines
and extends the knowledge about the regulation of DC migration.