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Glycobiology. 2018 Jun 1;28(6):406-417. doi: 10.1093/glycob/cwy025.

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

Author information

1
Complex Carbohydrate Research Center, University of Georgia, 315 Riverbend Road, Athens, GA 30602.
2
Department of Medicine, Division of Allergy and Clinical Immunology, The Johns Hopkins University School of Medicine, 5501 Hopkins Bayview Circle, Baltimore, MD 21224.
3
Department of Medicine, Division of Allergy-Immunology, Northwestern University Feinberg School of Medicine, 240 E. Huron Street, Room M-306, Chicago, IL 60611.
4
Department of Biochemistry and Molecular Biology, University of Georgia, B122 Life Sciences Building, Athens, GA 30602, USA.

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.

PMID:
29659839
PMCID:
PMC5967469
[Available on 2019-04-06]
DOI:
10.1093/glycob/cwy025
[Indexed for MEDLINE]

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