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

G. J. LaRosa, K. M. Thomas, M. E. Kaufmann, R. Mark, M. White, L. Taylor, G. Gray, D. Witt, J. Navarro

Research output: Contribution to journalArticle

130 Scopus citations

Abstract

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
Volume267
Issue number35
StatePublished - Jan 1 1992
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    LaRosa, G. J., Thomas, K. M., Kaufmann, M. E., Mark, R., White, M., Taylor, L., Gray, G., Witt, D., & Navarro, J. (1992). Amino terminus of the interleukin-8 receptor is a major determinant of receptor subtype specificity. Journal of Biological Chemistry, 267(35), 25402-25406.