Faculty Collaboration Database

Airway glycomic and allergic inflammatory consequences resulting from keratan sulfate galactose 6-O-sulfotransferase (CHST1) deficiency. Glycobiology 2018 Jun 01;28(6):406-417

Date

04/17/2018

Pubmed ID

29659839

Pubmed Central ID

PMC5967469

DOI

10.1093/glycob/cwy025

Scopus ID

2-s2.0-85048231573 (requires institutional sign-in at Scopus site)   16 Citations

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.

Author List

Kumagai T, Kiwamoto T, Brummet ME, Wu F, Aoki K, Zhu Z, Bochner BS, Tiemeyer M

Author

Kazuhiro Aoki PhD Associate Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Antigens, Differentiation, Myelomonocytic
Asthma
Lung
Lymphocytes
Macrophages
Mice
Mice, Inbred C57BL
Ovalbumin
Polysaccharides
Respiratory Mucosa
Sialic Acid Binding Immunoglobulin-like Lectins
Sulfotransferases