Cloning and characterization of a novel murine beta chemokine receptor, D6. Comparison to three other related macrophage inflammatory protein-1alpha receptors, CCR-1, CCR-3, and CCR-5

J Biol Chem. 1997 May 9;272(19):12495-504. doi: 10.1074/jbc.272.19.12495.


The beta-chemokine macrophage inflammatory protein-1alpha (MIP-1alpha) is chemotactic for many hemopoietic cell types and can inhibit hemopoietic stem cell (HSC) proliferation, effects mediated through G-protein coupled heptahelical receptors. We have isolated cDNAs for seven chemokine receptors, CCR-1 to -5, MIP-1alphaRL1, and a novel cDNA, D6. Chinese hamster ovary cells expressing CCR-1, -3, -5, and D6 bound 125I-murine MIP-1alpha: the order of affinity was D6 > CCR-5 > CCR-1 > CCR-3. Each bound a distinct subset of other beta-chemokines: the order of competition for 125I-murine MIP-1alpha on D6 was murine MIP-1alpha > human and murine MIP-1beta > human RANTES approximately JE > human MCP-3 > human MCP-1. Human MIP-1alpha and the alpha-chemokines did not compete. Like other chemokine receptors, D6 induced transient increases in [Ca2+] in HEK 293 cells upon ligand binding. D6 mRNA was abundant in lung and detectable in many other tissues. Bone marrow cell fractionation demonstrated T-cell and macrophage/monocyte expression of D6, and CCR-1, -3, and -5. Moreover, we could detect expression of CCR-3, CCR-5, and to a greater extent D6 in a cell population enriched for HSCs. Thus, we have characterized four murine beta chemokine receptors that are likely involved in mediating the pro-inflammatory functions of MIP-1alpha and other chemokines, and we present D6, CCR-3, and CCR-5 as candidate receptors in MIP-1alpha-induced HSC inhibition.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Bone Marrow / chemistry
  • CHO Cells
  • Chemokine CCL3
  • Chemokine CCL4
  • Cloning, Molecular
  • Cricetinae
  • DNA, Complementary / chemistry
  • Hematopoietic Stem Cells / chemistry
  • Humans
  • Macrophage Inflammatory Proteins / chemistry
  • Macrophage Inflammatory Proteins / genetics*
  • Mice
  • Molecular Sequence Data
  • Receptors, CCR10
  • Receptors, CCR3
  • Receptors, CCR5
  • Receptors, CCR8
  • Receptors, Chemokine*
  • Receptors, Cytokine / chemistry
  • Receptors, Cytokine / genetics*
  • Receptors, HIV / chemistry
  • Receptors, HIV / genetics*
  • Sequence Alignment


  • CCR3 protein, human
  • CCR8 protein, human
  • Ccr3 protein, mouse
  • Chemokine CCL3
  • Chemokine CCL4
  • DNA, Complementary
  • Macrophage Inflammatory Proteins
  • Receptors, CCR10
  • Receptors, CCR3
  • Receptors, CCR5
  • Receptors, CCR8
  • Receptors, Chemokine
  • Receptors, Cytokine
  • Receptors, HIV
  • chemokine receptor D6