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J Allergy Clin Immunol. 2014 Jan;133(1):240-7.e1-3. doi: 10.1016/j.jaci.2013.05.018. Epub 2013 Jul 2.

Mice deficient in the St3gal3 gene product α2,3 sialyltransferase (ST3Gal-III) exhibit enhanced allergic eosinophilic airway inflammation.

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Department of Medicine, Division of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, Md.
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Md.
Department of Biochemistry, Emory University School of Medicine, Atlanta, Ga.
Department of Medicine, Division of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, Md. Electronic address:



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.


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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