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 Scott Bochner, Michael Tiemeyer

Research output: Contribution to journalArticle

1 Citation (Scopus)

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

Fingerprint

Sialic Acid Binding Immunoglobulin-like Lectins
Glycomics
Keratan Sulfate
Sulfotransferases
Galactose
Ligands
Lung
Polysaccharides
Ovalbumin
Bronchoalveolar Lavage Fluid
Lymphocytes
Macrophages
Eosinophils
Inflammation
Tissue
carbohydrate sulfotransferases
Gene encoding
Neutrophils
Epithelium
Cell Count

Keywords

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

ASJC Scopus subject areas

  • Biochemistry

Cite this

Kumagai, Tadahiro ; Kiwamoto, Takumi ; Brummet, Mary E. ; Wu, Fan ; Aoki, Kazuhiro ; Zhu, Zhou ; Bochner, Bruce Scott ; Tiemeyer, Michael. / Airway glycomic and allergic inflammatory consequences resulting from keratan sulfate galactose 6-O-sulfotransferase (CHST1) deficiency. In: Glycobiology. 2018 ; Vol. 28, No. 6. pp. 406-417.
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Airway glycomic and allergic inflammatory consequences resulting from keratan sulfate galactose 6-O-sulfotransferase (CHST1) deficiency. / Kumagai, Tadahiro; Kiwamoto, Takumi; Brummet, Mary E.; Wu, Fan; Aoki, Kazuhiro; Zhu, Zhou; Bochner, Bruce Scott; Tiemeyer, Michael.

In: Glycobiology, Vol. 28, No. 6, 01.06.2018, p. 406-417.

Research output: Contribution to journalArticle

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AU - Kumagai, Tadahiro

AU - Kiwamoto, Takumi

AU - Brummet, Mary E.

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AU - Aoki, Kazuhiro

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AU - Bochner, Bruce Scott

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AB - 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.

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