Cloning of Complementary DNA Encoding a Functional Human Interleukin-8 Receptor

TLDR

Interleukin‑8 is a key inflammatory cytokine that stimulates neutrophil chemotaxis, degranulation, and respiratory burst through G‑protein‑coupled receptors that trigger intracellular calcium mobilization. A cDNA clone (p2) encoding a human IL‑8 receptor was isolated from HL‑60 neutrophils and, when expressed in Xenopus oocytes, bound 125I‑IL‑8 specifically and induced calcium mobilization with an EC50 of 20 nM.

Abstract

Interleukin-8 (IL-8) is an inflammatory cytokine that activates neutrophil chemotaxis, degranulation, and the respiratory burst. Neutrophils express receptors for IL-8 that are coupled to guanine nucleotide-binding proteins (G proteins); binding of IL-8 to its receptor induces the mobilization of intracellular calcium stores. A cDNA clone from HL-60 neutrophils, designated p2, has now been isolated that encodes a human IL-8 receptor. When p2 is expressed in oocytes from Xenopus laevis , the oocytes bind 125 I-labeled IL-8 specifically and respond to IL-8 by mobilizing calcium stores with an EC 50 of 20 nM. This IL-8 receptor has 77% amino acid identity with a second human neutrophil receptor isotype that binds IL-8 with higher affinity. It also exhibits 69% amino acid identity with a protein reported to be an N-formyl peptide receptor from rabbit neutrophils, but less than 30% identity with all other known G protein-coupled receptors, including the human N-formyl peptide receptor.