CLONING AND CHARACTERIZATION OF A NOVEL MURINE BETA-CHEMOKINE RECEPTOR, D6 - COMPARISON TO 3 OTHER RELATED MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA RECEPTORS, CCR-1, CCR-3, AND CCR-5
Rjb. Nibbs et al., CLONING AND CHARACTERIZATION OF A NOVEL MURINE BETA-CHEMOKINE RECEPTOR, D6 - COMPARISON TO 3 OTHER RELATED MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA RECEPTORS, CCR-1, CCR-3, AND CCR-5, The Journal of biological chemistry, 272(19), 1997, pp. 12495-12504
The beta-chemokine macrophage inflammatory protein-1 alpha (MIP-1 alph
a) is chemotactic for many hemopoietic cell types and can inhibit hemo
poietic stem cell (HSC) proliferation, effects mediated through G-prot
ein coupled heptahelical receptors. We have isolated cDNAs for seven c
hemokine receptors, CCR-1 to -5, MIP-1 alpha RL1, and a novel cDNA, D6
. Chinese hamster ovary cells expressing CCR-1, -3, -5, and D6 bound I
-125-murine MIP-1 alpha: the order of affinity was D6 > CCR-5 > CCR-1
> CCR-3. Each bound a distinct subset of other beta-chemokines: the or
der of competition for I-125-murine MIP-1 alpha on D6 was murine MIP-1
alpha > human and murine MIP-1 beta > human RANTES similar to JE > hu
man MCP-3 > human MCP-1. Human MIP-1 alpha and the alpha-chemokines di
d not compete. Like other chemokine receptors, He induced transient in
creases in [Ca2+] in HEK 293 cells upon ligand binding. D6 mRNA was ab
undant in lung and detectable in many other tissues, Bone marrow cell
fractionation demonstrated T-cell and macrophage/monocyte expression o
f D6, and CCR-1, -3, and -5. Moreover, we could detect expression of C
CR-3, CCR-5, and to a greater extent D6 in a cell population enriched
for HSCs. Thus, we have characterized four murine beta chemokine recep
tors that are likely involved in mediating the pro-inflammatory functi
ons of MIP-1 alpha and other chemokines, and we present D6, CCR-3, and
CCR-5 as candidate receptors in MIP-1 alpha-induced HSC inhibition.