Expression of ligands for Siglec-8 and Siglec-9 in human airways and airway cells

Yi Jia, Huifeng Yu, Steve M. Fernandes, Yadong Wei, Anabel Gonzalez-Gil, Mary G. Motari, Katarina Vajn, Whitney W. Stevens, Anju T. Peters, Bruce S. Bochner, Robert C. Kern, Robert P. Schleimer, Ronald L. Schnaar*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

Background Balanced activation and inhibition of the immune system ensures pathogen clearance while avoiding hyperinflammation. Siglecs, sialic acid-binding proteins found on subsets of immune cells, often inhibit inflammation: Siglec-8 on eosinophils and Siglec-9 on neutrophils engage sialoglycan ligands on airways to diminish ongoing inflammation. The identities of human siglec ligands and their expression during inflammation are largely unknown. Objective The histologic distribution, expression, and molecular characteristics of siglec ligands were explored in healthy and inflamed human upper airways and in a cellular model of airway inflammation. Methods Normal and chronically inflamed upper airway tissues were stained for siglec ligands. The ligands were extracted from normal and inflamed tissues and from human Calu-3 cells for quantitative analysis by means of siglec blotting and isolation by means of siglec capture. Results Siglec-8 ligands were expressed on a subpopulation of submucosal gland cells of human inferior turbinate, whereas Siglec-9 ligands were expressed more broadly (submucosal glands, epithelium, and connective tissue); both were significantly upregulated in patients with chronic rhinosinusitis. Human airway (Calu-3) cells expressed Siglec-9 ligands on mucin 5B (MUC5B) under inflammatory control through the nuclear factor κB pathway, and MUC5B carried sialoglycan ligands of Siglec-9 on human upper airway tissue. Conclusion Inflammation results in upregulation of immune-inhibitory Siglec-8 and Siglec-9 sialoglycan ligands on human airways. Siglec-9 ligands are upregulated through the nuclear factor κB pathway, resulting in their enhanced expression on MUC5B. Siglec sialoglycan ligand expression in inflamed cells and tissues may contribute to the control of airway inflammation.

Original languageEnglish (US)
Pages (from-to)799-810.e7
JournalJournal of Allergy and Clinical Immunology
Volume135
Issue number3
DOIs
StatePublished - Mar 1 2015

Keywords

  • Chronic rhinosinusitis
  • glycobiology
  • inflammation
  • mucin 5B
  • nuclear factor κB
  • siglecs
  • submucosal gland cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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