STRUCTURE AND FUNCTIONAL EXPRESSION OF THE HUMAN MACROPHAGE INFLAMMATORY PROTEIN 1-ALPHA RANTES RECEPTOR

The chemokine beta family is comprised of at least six distinct cytoki nes that regulate trafficking of phagocytes and lymphocytes in mammali an species; at least one of these, macrophage inflammatory protein 1al pha (MIP-1alpha), also regulates the growth of hematopoietic stem cell s. We now show that MIP-1alpha and the related beta chemokine, R-ANTES , induce transient alterations in intracellular Ca2+ Concentration in polymorphonuclear leukocytes that can be reciprocally and specifically desensitized, suggesting a common receptor. Moreover, we have now clo ned both the cDNA and the gene for this receptor, functionally express ed the receptor in Xenopus oocytes, and mapped the gene to human chrom osome 3p21. Transcripts for the receptor were found in mature and imma ture myeloid cells as well as B cells. The receptor is a member of the G protein-coupled receptor superfamily. It has approximately 33% amin o acid identity with receptors for the alpha chemokine, interleukin 8, and may be the human homologue of the product of US28, an open readin g frame of human cytomegalovirus.