Molecular Cloning and Expression of a Novel Rat CC-Chemokine Receptor (rCCR10rR) That Binds MCP-1 and MIP-1β with High Affinity

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Abstract
Chemokines stimulate the migration and activation of leukocytes to areas of inflammation or tissue damage by binding to specific seven-transmembrane G protein-coupled receptors. We report the cloning of a novel rat CC-chemokine receptor, the rat CCR10-related receptor (rCCR10rR), with 72% amino acid identity to the human CC-chemokine receptor CCR10 and 30%-35% amino acid identity to the known human CC-chemokine receptors CCR1, CCR2, CCR3, CCR4, and CCR5. Multiple tissue northern analysis indicates that rCCR10rR is expressed at a higher level in spleen than in the other tissues assayed. The CC-chemokines MIP-1β and MCP-1 bind with highest affinity to rCCR10rR, with KD = 0.4 and 0.7 nM, respectively. The CC-chemokines RANTES and MIP-1α were poor competitors for MIP-1β binding, with IC50 values of 150 nM and 86 nM, respectively, but the KD for RANTES binding was still in the nanamolar range (4.8 nM). These results indicate that rCCR10rR is a true member of the CC-chemokine receptor family and may be involved in eliciting the responses to the CC-chemokines MIP-1β and MCP-1.