Genomic organisation and biological characterization of the novel human CC chemokine DC-CK-1/PARC/MIP-4/SCYA18

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dc.contributor.authorGuan, P.
dc.contributor.authorBurghes, A.
dc.contributor.authorCunningham, A.
dc.contributor.authorLira, P.
dc.contributor.authorBrissette, W.
dc.contributor.authorNeote, K.
dc.contributor.authorMcColl, S.
dc.date.issued1999
dc.description.abstractThe 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.
dc.identifier.citationGenomics, 1999; 56(3):296-302
dc.identifier.doi10.1006/geno.1998.5635
dc.identifier.issn0888-7543
dc.identifier.issn1089-8646
dc.identifier.orcidMcColl, S. [0000-0003-0949-4660]
dc.identifier.urihttp://hdl.handle.net/2440/11576
dc.language.isoen
dc.publisherACADEMIC PRESS INC
dc.source.urihttps://doi.org/10.1006/geno.1998.5635
dc.subjectPeritoneum
dc.subjectEosinophils
dc.subjectNeutrophils
dc.subjectLeukocytes, Mononuclear
dc.subjectCD4-Positive T-Lymphocytes
dc.subjectCD8-Positive T-Lymphocytes
dc.subjectChromosomes, Artificial, Yeast
dc.subjectChromosomes, Human, Pair 17
dc.subjectAnimals
dc.subjectMice, Inbred BALB C
dc.subjectHumans
dc.subjectMice
dc.subjectCalcium
dc.subjectRecombinant Proteins
dc.subjectChemokines
dc.subjectChemokines, CC
dc.subjectChemokines, CXC
dc.subjectFlow Cytometry
dc.subjectSpectrometry, Fluorescence
dc.subjectAmino Acid Sequence
dc.subjectBase Sequence
dc.subjectModels, Genetic
dc.subjectMolecular Sequence Data
dc.subjectMale
dc.subjectChemokine CXCL12
dc.subjectLeukocyte Common Antigens
dc.titleGenomic organisation and biological characterization of the novel human CC chemokine DC-CK-1/PARC/MIP-4/SCYA18
dc.typeJournal article
pubs.publication-statusPublished

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