Kiwamoto T, Brummet ME, Wu F, Motari MG, Smith DF, Schnaar RL, Zhu Z, Bochner BS. (2013) Mice deficient in the St3gal3 gene product α2,3 sialyltransferase (ST3Gal-III) exhibit enhanced allergic eosinophilic airway inflammation. J Allergy Clin Immunol. 133(1):240-7.e1-3. PMID: 23830412 PMCID: PMC3874253.
Sialic acid-binding immunoglobulin-like lectin (Siglec)-F is a proapoptotic receptor on mouse eosinophils, but little is known about its natural tissue ligand.
We previously reported that the St3gal3 gene product α2,3 sialyltransferase (ST3Gal-III) is required for constitutive Siglec-F lung ligand synthesis. We therefore hypothesized that attenuation of ST3Gal-III will decrease Siglec-F ligand levels and enhance allergic eosinophilic airway inflammation.
C57BL/6 wild-type mice and St3gal3 heterozygous or homozygous deficient (St3gal3+/- and St3gal3-/-) mice were used. Eosinophilic airway inflammation was induced through sensitization to ovalbumin (OVA) and repeated airway OVA challenge. Siglec-F human IgG1 fusion protein (Siglec-F-Fc) was used to detect Siglec-F ligands. Lung tissue and bronchoalveolar lavage fluid (BALF) were analyzed for inflammation, as well as various cytokines and chemokines. Serum was analyzed for allergen-specific immunoglobulin levels.
Western blotting with Siglec-F-Fc detected approximately 500-kDa and approximately 200-kDa candidate Siglec-F ligands that were less abundant in St3gal3+/- lung extracts and nearly absent in St3gal3-/- lung extracts. After OVA sensitization and challenge, Siglec-F ligands were increased in wild-type mouse lungs but less so in St3gal3 mutants, whereas peribronchial and BALF eosinophil numbers were greater in the mutants, with the following rank order: St3gal3-/- ≥ St3gal3+/- > wild-type mice. Levels of various cytokines and chemokines in BALF were not significantly different among these 3 types of mice, although OVA-specific serum IgG1 levels were increased in St3gal3-/- mice.
After OVA sensitization and challenge, St3gal3+/- and St3gal3-/- mice have more intense allergic eosinophilic airway inflammation and less sialylated Siglec-F ligands in their airways. One possible explanation for these findings is that levels of sialylated airway ligands for Siglec-F might be diminished in mice with attenuated levels of ST3Gal-III, resulting in a reduction in a natural proapoptotic pathway for controlling airway eosinophilia.
Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
6’-su-sLacNAc, 6′-Sulfated sialyl Lewis X, 6′-Sulfated sialyl N-acetyl-D-lactosamine, 6′-su-sLe(x), 6′-sulfated sialyl Lewis X, 6′-sulfated sialyl N-acetyl-D-lactosamine, BALF, Bronchoalveolar lavage fluid, Eosinophils, MBP, Major basic protein, OVA, Ovalbumin, ST3Gal-III, Sialic acid–binding immunoglobulin-like lectin, Siglec, Siglec-8 human IgG(1) Fc chimera, Siglec-8-Fc, Siglec-F, Siglec-F human IgG(1) Fc chimera, Siglec-F-Fc, St3gal3, St3gal3 gene product α2,3 sialyltransferase, WT, Wild-type, apoptosis, asthma, glycan ligands, lung
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