MOLECULAR-CLONING AND FUNCTIONAL EXPRESSION OF A NOVEL CC-CHEMOKINE RECEPTOR CDNA FROM A HUMAN BASOPHILIC CELL-LINE

We report the cloning and characterization of a novel basophil CC chem okine receptor, K5-5, from the human immature basophilic cell line KU- 812. The predicted protein sequence of K5-5 shows only 49% identity to the macrophage inflammatory protein-1 alpha/RANTES receptor (CC CKR-1 ) and 47% identity to monocyte chemotactic protein-1 receptor (b form) , suggesting that this cDNA encodes a novel member of the CC chemokine receptor family. Analysis of K5-5 mRNA expression indicates that it i s restricted to leukocyte-rich tissues, In addition, we have shown sig nificant levels of K5-5 mRNA in human basophils, which were up-regulat ed by treatment with interleukin-5. The CC chemokines, macrophage infl ammatory protein-1 alpha, RANTES, and monocyte chemotactic protein-1 w ere able to stimulate a Ca2+-activated chloride channel in Xenopus lae vis oocytes injected with R5-5 cRNA, whereas no signal was detected in response to monocyte chemotactic protein-2, macrophage inflammatory p rotein-1 beta, or the CXC chemokine, interleukin-8. Taken together, th ese results indicate for the first time the presence of a CC chemokine receptor on basophils, which functions as a ''shared'' CC chemokine r eceptor and may therefore be implicated in the pathogenesis of basophi l-mediated allergic diseases.