CLONING AND FUNCTIONAL EXPRESSION OF A HUMAN EOSINOPHIL CC-CHEMOKINE RECEPTOR

Eosinophils undergo chemotaxis, degranulate, and exhibit [Ca2+](i) cha nges in response to the human CC chemokines macrophage inflammatory pr otein (MLP)-1 alpha, regulated on activation, normal T expressed and s ecreted (RANTES), and monocyte chemoattractant protein-3 (MCP-3), but the receptors involved have not been defined. We have isolated a human cDNA encoding the first eosinophil-selective chemokine receptor, desi gnated GC chemokine receptor 3 (CC CKR3). CC CKR3 is a seven-transmemb rane domain G protein-coupled receptor most closely related to the pre viously reported monocyte- and neutrophil-selective receptor CC CKR1 ( also known as the MIP-1 alpha/RANTES receptor). When [Ca2+](i) changes were monitored in stably transfected human embryonic kidney 293 cells , MIP-1 alpha and RANTES were both potent agonists for CC CKR3 and CC CKR1. However, MIP-1 beta was also an agonist for CC CKR3 but not CC C KR1; MCP-3 was an agonist for CC CKR1 but not CC CKR3, CC CKR3 may be one of the host factors responsible for selective recruitment of eosin ophils to sites of inflammation.