Amino terminus of the interleukin-8 receptor is a major determinant of receptor subtype specificity

Gregory J. LaRosa, Kathleen M. Thomas, Mark E. Kaufmann, Robert Mark, Michael White, Linda Taylor, Gary Gray, Daniel Witt, Javier Navarro

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159 Scopus citations


Interleukin-8 (IL-8) is a key mediator in the migration of neutrophils from the circulation to the site of inflammation in the tissue. IL-8 is secreted by many cell types in response to proinflammatory stimuli such as interleukin 1, tumor necrosis factor, and lipopolysaccharide and is a potent chemoattractant and activator of neutrophils. Neutrophil activating peptide-2 (NAP-2) and melanoma growth-stimulatory activity (MGSA/GRO) are structurally and functionally related to IL-8 and, like IL-8, bind to specific G protein-coupled receptors on neutrophils. In the present study two closely related cloned IL-8 receptor subtypes are characterized by expression of the cDNA clones in monkey kidney cells (COS-7) or Chinese hamster ovary cells and analysis of their ligand binding profiles. Both receptor subtypes bind 125I-labeled IL-8 with similar high affinity, however, the F3R receptor binds IL-8 exclusively, while the 4Ab receptor binds both IL-8 and MGSA/GRO with high affinity and NAP-2 with lesser affinity. Furthermore, we demonstrate with the use of intersubtype chimeric receptors that the specificity of ligand binding to both IL-8 receptor subtypes is dictated by the heterogeneous NH2-terminal domain. The F3R receptor is representative of a restricted IL-8 receptor subtype, and 4Ab represents a nonrestricted receptor subtype. It is proposed that these subtypes be named IL-8 receptors α and β, respectively.

Original languageEnglish (US)
Pages (from-to)25402-25406
Number of pages5
JournalJournal of Biological Chemistry
Issue number35
StatePublished - Dec 15 1992

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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