IL-8 released constitutively by primary bronchial epithelial cells in culture forms an inactive complex with secretory component

Lindsay J. Marshall, Beatrice Perks, Thomas Ferkol, Janis K. Shute

Research output: Contribution to journalArticlepeer-review

Abstract

The bronchial epithelium is a source of both α and β chemokines and, uniquely, of secretory component (SC), the extracellular ligand-binding domain of the polymeric IgA receptor. Ig superfamily relatives of SC, such as IgG and α2-macroglobulin, bind IL-8. Therefore, we tested the hypothesis that SC binds IL-8, modifying its activity as a neutrophil chemoattractant. Primary bronchial epithelial cells were cultured under conditions to optimize SC synthesis. The chemokines IL-8, epithelial neutrophil-activating peptide-78, growth-related oncogene α, and RANTES were released constitutively by epithelial cells from both normal and asthmatic donors and detected in high m.w. complexes with SC. There were no qualitative differences in the production of SC-chemokine complexes by epithelial cells from normal or asthmatic donors, and in all cases this was the only form of chemokine detected. SC contains 15% N-linked carbohydrate, and complete deglycosylation with peptide N-glycosidase F abolished IL-8 binding. In micro-Boyden chamber assays, no IL-8-dependent neutrophil chemotactic responses to epithelial culture supernatants could be demonstrated. SC dose-dependently (IC50 ∼0.3 nM) inhibited the neutrophil chemotactic response to rIL-8 (10 nM) in micro-Boyden chamber assays and also inhibited IL-8-mediated neutrophil transendothelial migration. SC inhibited the binding of IL-8 to nonspecific binding sites on polycarbonate filters and endothelial cell monolayers, and therefore the formation of haptotactic gradients, without effects on IL-8 binding to specific receptors on neutrophils. The data indicate that in the airways IL-8 may be solubilized and inactivated by binding to SC

Original languageEnglish
Pages (from-to)2816-2823
Number of pages8
JournalJournal of Immunology
Volume167
Issue number5
DOIs
Publication statusPublished - 1 Sep 2001

Keywords

  • asthma
  • binding sites
  • bronchi
  • cultured cells
  • chemokines
  • leukocyte chemotaxis
  • epithelial cells
  • glycosylation
  • humans
  • interleukin-8
  • macromolecular substances
  • molecular weight
  • neutrophils
  • secretory component
  • signal transduction

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