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Genomic organization and biological characterization of the novel human CC chemokine DC-CK-1/PARC/MIP-4/SCYA18.
Guan P; Burghes AH; Cunningham A; Lira P; Brissette WH; Neote K; McColl
July 30, 1999
Unique Identifier : AIDSLINE MED/99189237

The chemokines are a group of chemotactic molecules that appear to regulate the directed movement of white blood cells in vitro and in vivo and may therefore play important roles in inflammation and immunity. The genes encoding the chemokines are clustered in close physical proximity to each other. A large cluster of human CC chemokine genes resides on chromosome 17. We have used this information in a positional cloning approach to identify novel chemokine genes within this cluster. We constructed a YAC contig encompassing the MIP-1alpha (HGMW-approved symbol SCYA3) gene region and used exon trapping and sequence analysis to isolate novel chemokine genes. Using this approach, a gene encoding a chemokine named MIP-4, based on its homology with MIP-1alpha (49.5% identity at the nucleotide level and 59.6% at the predicted amino acid level), was found. The MIP-4 gene (HGMW-approved symbol SCYA18) consists of three exons spread over 7.1 kb and is separated from the MIP-1alpha gene by 16 kb. The MIP-4 gene encodes a 750-bp mRNA that is expressed in lung and macrophages but not in brain or muscle. The mRNA encodes an 89-amino-acid protein and includes a predicted signal peptide of 21 amino acids. Recombinant or synthetic MIP-4 induced calcium mobilization in naive and activated T lymphocyte subpopulations in vitro. Injection of synthetic MIP-4 into the peritoneal cavity of mice led to the accumulation of both CD4(+) and CD8(+) T lymphocytes, but not monocytes or granulocytes. These observations provide new information concerning the arrangement of the CC chemokine gene cluster on human chromosome 17 and indicate that the MIP-4 gene product is chemotactic in vivo for both CD4(+) and CD8(+) T lymphocytes and may therefore be implicated in both humoral and cell-mediated immunity. Copyright 1999 Academic Press.

JOURNAL ARTICLE Amino Acid Sequence Animal Antigens, CD45/DRUG EFFECTS Base Sequence Calcium/METABOLISM Chemokines/*GENETICS/*METABOLISM Chemokines, CC/*GENETICS/*METABOLISM/PHARMACOLOGY Chemokines, CXC/PHARMACOLOGY Chromosomes, Human, Pair 17/*GENETICS Chromosomes, Yeast Artificial CD4-Positive T-Lymphocytes/DRUG EFFECTS CD8-Positive T-Lymphocytes/DRUG EFFECTS Eosinophils/DRUG EFFECTS Flow Cytometry Human Leukocytes, Mononuclear/DRUG EFFECTS Male Mice Mice, Inbred BALB C Models, Genetic Molecular Sequence Data Neutrophils/DRUG EFFECTS Peritoneum/METABOLISM Recombinant Proteins/GENETICS Spectrometry, Fluorescence Support, Non-U.S. Gov't