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Chemoattractant for Human Neutrophils and Dendritic Cells1
Department of Immunology and Shanghai Brilliance Biotechnology Institute, Second Military Medical University, Shanghai, Peoples Republic of China
Chemokines play important roles in leukocyte trafficking as well as
function regulation. In this study, we described the identification and
characterization of a novel CXC chemokine from a human dendritic cell
(DC) cDNA library, the full-length cDNA of which contains an open
reading frame encoding 111 aa with a putative signal peptide of 34 aa.
This CXC chemokine shares greatest homology with macrophage
inflammatory protein (MIP)-2
ß, hence is designated as MIP-2
.
Mouse MIP-2
was identified by electrocloning and is highly
homologous to human MIP-2
. Northern blotting revealed that MIP-2
was constitutively and widely expressed in most normal tissues with the
greatest expression in kidney, but undetectable in most tumor cell
lines except THP-1 cells. In situ hybridization analysis demonstrated
that MIP-2
was mainly expressed by the epithelium of tubules in the
kidney and hepatocytes in the liver. Although no detectable expression
was observed in freshly isolated or PMA-treated monocytes, RT-PCR
analysis revealed MIP-2
expression by monocyte-derived DC.
Recombinant MIP-2
from 293 cells is about 9.5 kDa in size and
specifically detectable by its polyclonal Ab developed by the
immunization with its 6His-tagged fusion protein. The eukaryotically
expressed MIP-2
is a potent chemoattractant for neutrophils, and
weaker for DC, but inactive to monocytes, NK cells, and T and B
lymphocytes. Receptor binding assays showed that MIP-2
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.
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