CLONING AND FUNCTIONAL EXPRESSION OF CC-CKR5, A HUMAN MONOCYTE CC-CHEMOKINE RECEPTOR-SELECTIVE FOR MIP-1-ALPHA, MIP-1-BETA, AND RANTES

We have cloned a human cDNA for a novel CC chemokine receptor (CC CKR) designated CC CKR5 that has 48-75% amino acid identity to other CC CK Rs, CC CKR5 mRNA was detected constitutively in primary adherent monoc ytes but not in primary neutrophils or eosinophils, Macrophage inflamm atory protein-1 alpha (MIP-1 alpha), MIP-1 beta, and RANTES were all p otent agonists for CC CKR5 (EC(50) = 3-30 nM) when calcium flux was me asured in transfected HEK 293 cells, yet the apparent binding affiniti es of the corresponding iodinated chemokines to intact cells expressin g the receptor were low (IC50 similar to 100 nM). The calcium flux res ponses were completely blocked by treatment of transfected cells with pertussis toxin, These data suggest that CC CKR5 is a G(i)-coupled rec eptor that may mediate monocyte responses to MIP-1 alpha, MIP-1 beta, and RANTES.