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 language | English (US) |
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Pages (from-to) | 406-417 |
Number of pages | 12 |
Journal | Glycobiology |
Volume | 28 |
Issue number | 6 |
DOIs | |
State | Published - Jun 1 2018 |
Keywords
- CHST1
- O-glycan
- Siglec-F
- asthma
- eosinophils
ASJC Scopus subject areas
- General Medicine