title: Cloning and characterization of a specific receptor for the novel CC chemokine MIP-3alpha from lung dendritic cells.
abstract: Dendritic cells are potent antigen-presenting cells involved in the initiation of immune responses. The trafficking of these cells to tissues and lymph nodes is mediated by members of the chemokine family. Recently, a novel CC chemokine known as MIP-3alpha or liver and activation-regulated chemokine has been identified from the EMBL/GenBank/DDBJ expressed sequence tag database. In the present study, we have shown that the messenger RNA for MIP-3alpha is expressed predominantly in inflamed and mucosal tissues. MIP-3alpha produced either synthetically or by human embryonic kidney 293 cells is chemotactic for CD34(+)-derived dendritic cells and T cells, but is inactive on monocytes and neutrophils. MIP-3alpha was unable to displace the binding of specific CC or CXC chemokines to stable cell lines expressing their respective high affinity receptors, namely CCR1-5 and CXCR1 and CXCR2, suggesting that MIP-3alpha acts through a novel CC chemokine receptor. Therefore, we used degenerate oligonucleotide-based reverse transcriptase PCR to identify candidate MIP-3alpha receptors in lung dendritic cells. Our results show that the orphan receptor known as GCY-4, CKRL-3, or STRL-22 is a specific receptor for MIP-3alpha, and that its activation leads to pertussis toxin-sensitive and phospholipase C-dependent intracellular Ca2+ mobilization when it is expressed in HEK 293 cells.
authors.affiliation: Geneva Biomedical Research Institute, GlaxoWellcome Research and Development, Geneva, Switzerland. CAP15123@ggr.co.uk
authors.forename: C A
authors.initials: CA
authors.lastname: Power
authors.forename: D J
authors.initials: DJ
authors.lastname: Church
authors.forename: A
authors.initials: A
authors.lastname: Meyer
authors.forename: S
authors.initials: S
authors.lastname: Alouani
authors.forename: A E
authors.initials: AE
authors.lastname: Proudfoot
authors.forename: I
authors.initials: I
authors.lastname: Clark-Lewis
authors.forename: S
authors.initials: S
authors.lastname: Sozzani
authors.forename: A
authors.initials: A
authors.lastname: Mantovani
authors.forename: T N
authors.initials: TN
authors.lastname: Wells
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D001667:Binding, Competitive; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D054418:Chemokine CCL20; D019742:Chemokines, CC; D003001:Cloning, Molecular; D017931:DNA Primers / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D008168:Lung / Q000276:immunology* / Q000378:metabolism; D019402:Macrophage Inflammatory Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D054399:Receptors, CCR6; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000235:genetics* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: C108355:CCL20 protein, human; C106311:CCR6 protein, human; D054418:Chemokine CCL20; D019742:Chemokines, CC; D017931:DNA Primers; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger; D054399:Receptors, CCR6; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D002118:Calcium