Molecular characterization of two murine eosinophil beta chemokine receptors.
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.
Post
T W
TW
Department of Medicine, Brigham and Women's Hospital, Beth Israel Hospital, Boston, MA, USA.
Bozic
C R
CR
Rothenberg
M E
ME
Luster
A D
AD
Gerard
N
N
Gerard
C
C
D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D015139:Blotting, Southern; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D004804:Eosinophils / Q000378:metabolism*; D006801:Humans; D015848:Interleukin-5 / Q000235:genetics; D019402:Macrophage Inflammatory Proteins; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D015846:Monokines / Q000378:metabolism; D018121:Receptors, Cytokine / Q000378:metabolism*
D054407:Chemokine CCL4; D018946:Chemokine CCL5; D018925:Chemokines; D016207:Cytokines; D015848:Interleukin-5; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D018121:Receptors, Cytokine