Airway glycomic and allergic inflammatory consequences resulting from keratan sulfate galactose 6-O-sulfotransferase (CHST1) deficiency

Tadahiro Kumagai, Takumi Kiwamoto, Mary E. Brummet, Fan Wu, Kazuhiro Aoki, Zhou Zhu, Bruce S. Bochner, Michael Tiemeyer

Research output: Contribution to journalArticle

Abstract

Siglec-F is a pro-Apoptotic receptor on mouse eosinophils that recognizes 6?-sulfated sialyl Lewis X and 6?-sulfated sialyl N-Acetyl-lactosamine as well as multivalent sialyl N-Acetyl-lactosamine structures on glycan arrays. We hypothesized that attenuation of the carbohydrate sulfotransferase 1 (CHST1) gene encoding keratan sulfate galactose 6-O-sulfotransferase, an enzyme likely required for 6?-sulfation of some of these putative Siglec-F glycan ligands, would result in decreased Siglec-F lung ligand levels and enhanced allergic eosinophilic airway inflammation. Tissue analysis detected CHST1 expression predominantly not only in parenchymal cells but not in airway epithelium, the latter being a location where Siglec-F ligands are located. Western blotting of lung extracts with Siglec-F-Fc fusion proteins detected ?500 kDa and ?200 kDa candidate Siglec-F ligands that were not appreciably altered in CHST1-/-lungs compared with normal mouse lungs. Characterization of the O-linked glycans of lung tissue and bronchoalveolar lavage fluid detected altered sialylation but minimal change in sulfation. Eosinophilic airway inflammation was induced in wild-Type (WT) and CHST1-/-mice via sensitization to ovalbumin (OVA) and repeated airway challenge. After OVA sensitization and challenge, Siglec-F ligands on airway cells, and numbers of eosinophils and neutrophils accumulating in the airways, both increased to a similar degree in WT and CHST1-/-mouse lungs, while macrophages and lymphocytes increased significantly more in CHST1-/-mouse airway compared with normal mouse lungs. Therefore, keratan sulfate galactose 6-O-sulfotransferase does not contribute to the synthesis of glycan ligands for Siglec-F in the airways, although its absence results in exaggerated accumulation of airway macrophages and lymphocytes.

Original languageEnglish (US)
Pages (from-to)406-417
Number of pages12
JournalGlycobiology
Volume28
Issue number6
DOIs
StatePublished - Jun 1 2018

Keywords

  • asthma
  • CHST1
  • eosinophils
  • O-glycan
  • Siglec-F

ASJC Scopus subject areas

  • Biochemistry

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