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

Research output: Contribution to journalArticle

130 Citations (Scopus)

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 - Dec 15 1992
Externally publishedYes

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Interleukin-8 Receptors
Interleukin-8
Neutrophils
Ligands
COS Cells
Chemotactic Factors
G-Protein-Coupled Receptors
Cricetulus
Interleukin-1
Haplorhini
Lipopolysaccharides
Ovary
Melanoma
Complementary DNA
Clone Cells
Tumor Necrosis Factor-alpha
Cells
Tissue
Inflammation
Kidney

ASJC Scopus subject areas

  • Biochemistry

Cite this

LaRosa, G. J., Thomas, K. M., Kaufmann, M. E., Mark, R., White, M., Taylor, L., ... 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.

Amino terminus of the interleukin-8 receptor is a major determinant of receptor subtype specificity. / LaRosa, Gregory J.; Thomas, Kathleen M.; Kaufmann, Mark E.; Mark, Robert; White, Michael; Taylor, Linda; Gray, Gary; Witt, Daniel; Navarro, Javier.

In: Journal of Biological Chemistry, Vol. 267, No. 35, 15.12.1992, p. 25402-25406.

Research output: Contribution to journalArticle

LaRosa, GJ, Thomas, KM, Kaufmann, ME, 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, vol. 267, no. 35, pp. 25402-25406.
LaRosa GJ, Thomas KM, Kaufmann ME, Mark R, White M, Taylor L et al. Amino terminus of the interleukin-8 receptor is a major determinant of receptor subtype specificity. Journal of Biological Chemistry. 1992 Dec 15;267(35):25402-25406.
LaRosa, Gregory J. ; Thomas, Kathleen M. ; Kaufmann, Mark E. ; Mark, Robert ; White, Michael ; Taylor, Linda ; Gray, Gary ; Witt, Daniel ; Navarro, Javier. / Amino terminus of the interleukin-8 receptor is a major determinant of receptor subtype specificity. In: Journal of Biological Chemistry. 1992 ; Vol. 267, No. 35. pp. 25402-25406.
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