Molecular characterization of two murine eosinophil beta chemokine receptors

J Immunol. 1995 Dec 1;155(11):5299-305.

Abstract

beta or C-C chemokines including RANTES, MCP-3, MIP-1 alpha, and eotaxin have been implicated in the pathogenesis of eosinophilic inflammation. Two human beta chemokine receptors have been cloned and characterized: the MIP-1 alpha/RANTES receptor or C-C chemokine receptor 1 (CCR-1) and the MCP-1 receptor or C-C chemokine receptor 2 (CCR-2). However, no murine beta chemokine receptors have thus far been reported. Molecular cloning from mouse genomic DNA and cDNA libraries yielded two murine beta chemokine receptors with 79% and 65% sequence identity with human CCR-1, and 50% and 55% with human CCR-2. COS cells transiently transfected with the murine homologue of human CCR-1 bind murine MIP-1 alpha and human RANTES with Kds of 3.4 nM and 4.2 nM and murine MIP-1 beta with an EC50 of 8.9 nM. The other murine beta chemokine receptor, which we have designated murine CCR-3, also binds murine MIP-1 alpha. The mRNAs for both receptors are expressed in eosinophils from IL-5 transgenic mice. The level of murine CCR-3 mRNA in these mouse eosinophils exceeds that of CCR-1 mRNA and approaches actin levels. Murine MIP-1 alpha was found to be a potent chemoattractant for murine eosinophils. Our findings suggest that the murine MIP-1 alpha ligand/receptor system is an important mediator of murine eosinophil trafficking.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Blotting, Northern
  • Blotting, Southern
  • Chemokine CCL4
  • Chemokine CCL5 / metabolism
  • Chemokines / metabolism*
  • Cytokines / metabolism
  • Eosinophils / metabolism*
  • Humans
  • Interleukin-5 / genetics
  • Macrophage Inflammatory Proteins
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data
  • Monokines / metabolism
  • Receptors, Cytokine / metabolism*

Substances

  • Chemokine CCL4
  • Chemokine CCL5
  • Chemokines
  • Cytokines
  • Interleukin-5
  • Macrophage Inflammatory Proteins
  • Monokines
  • Receptors, Cytokine

Associated data

  • GENBANK/U29677
  • GENBANK/U29678