Cloning and characterization of a specific receptor for the novel CC chemokine MIP-3alpha from lung dendritic cells

J Exp Med. 1997 Sep 15;186(6):825-35. doi: 10.1084/jem.186.6.825.


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.

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Binding, Competitive
  • Calcium / metabolism
  • Cell Line
  • Chemokine CCL20
  • Chemokines, CC*
  • Cloning, Molecular
  • DNA Primers / genetics
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Gene Expression
  • Humans
  • Lung / immunology*
  • Lung / metabolism
  • Macrophage Inflammatory Proteins / genetics
  • Macrophage Inflammatory Proteins / metabolism*
  • Molecular Sequence Data
  • Polymerase Chain Reaction
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, CCR6
  • Receptors, Chemokine*
  • Receptors, Cytokine / genetics*
  • Receptors, Cytokine / metabolism
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism


  • CCL20 protein, human
  • CCR6 protein, human
  • Chemokine CCL20
  • Chemokines, CC
  • DNA Primers
  • Macrophage Inflammatory Proteins
  • RNA, Messenger
  • Receptors, CCR6
  • Receptors, Chemokine
  • Receptors, Cytokine
  • Calcium

Associated data

  • GENBANK/P25024
  • GENBANK/P25025
  • GENBANK/P32246
  • GENBANK/P32248
  • GENBANK/P41597
  • GENBANK/P49682
  • GENBANK/P51677
  • GENBANK/P51679
  • GENBANK/P51681
  • GENBANK/Q16570
  • GENBANK/Q28474
  • GENBANK/U28934
  • GENBANK/U45983
  • GENBANK/U45984
  • GENBANK/U95626
  • GENBANK/X68149