THE MURINE INTERLEUKIN-8 TYPE-B RECEPTOR HOMOLOG AND ITS LIGANDS - EXPRESSION AND BIOLOGICAL CHARACTERIZATION

KC, the product of an immediate early gene induced in mouse fibroblast s by platelet derived growth factor, was synthesized as a recombinant protein in Escherichia coli and binds with 0.8 nM affinity to mouse ne utrophils. Human neutrophils also bind recombinant KC at a site compet itive with human interleukin (IL8) and Gro-alpha/ MGSA, consistent wit h binding at the IL8 type B receptor (IL8RB). The cDNA corresponding t o human IL8RB hybridizes strongly with two restriction fragments in mu rine genomic DNA, representing candidate receptor genes for KC, Molecu lar cloning of both mouse genomic DNA and neutrophil exudate cell cDNA libraries yielded a receptor with similar to 68% sequence identity to both the human IL8 type A and B receptors. Transient expression of th e murine receptor cDNA in COS cells conferred binding ability to KC an d a related gene product, macrophage inflammatory protein-2 (MIP-2) wi th high affinity (similar to 5 nM). Human IL8 was a poor agonist for t his expressed receptor (K-d = similar to 400 nM). The potent activity of human IL8 on mouse polymorphonuclear neutrophils is not consistent with binding on the cloned receptor and suggests that murine homologue s of IL8 and an IL8 type A receptor remain to be identified. Our data indicate that KC is the murine homologue of human Gro-alpha, and the K C receptor is an ILS type B receptor homologue capable of binding both KC and macrophage inflammatory protein-2 with high affinity.