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

Takumi Kiwamoto, Mary E. Brummet, Fan Wu, Mary G. Motari, David F. Smith, Ronald L. Schnaar, Zhou Zhu, Bruce S. Bochner

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Background Sialic acid-binding immunoglobulin-like lectin (Siglec)-F is a proapoptotic receptor on mouse eosinophils, but little is known about its natural tissue ligand. Objective 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. Methods 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. Results 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 IgG 1 levels were increased in St3gal3-/- mice. Conclusions 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.

Original languageEnglish (US)
JournalJournal of Allergy and Clinical Immunology
Volume133
Issue number1
DOIs
StatePublished - Jan 1 2014

Fingerprint

beta-galactoside alpha-2,3-sialyltransferase
Sialic Acid Binding Immunoglobulin-like Lectins
Sialyltransferases
Inflammation
Ovalbumin
Ligands
Genes
Bronchoalveolar Lavage Fluid
Lung
Chemokines
Eosinophils
Immunoglobulin G
Cytokines

Keywords

  • 6′-sulfated sialyl Lewis X
  • 6′-sulfated sialyl N-acetyl-D-lactosamine
  • Eosinophils
  • Siglec-F
  • St3gal3
  • apoptosis
  • asthma
  • glycan ligands
  • lung

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Kiwamoto, Takumi ; Brummet, Mary E. ; Wu, Fan ; Motari, Mary G. ; Smith, David F. ; Schnaar, Ronald L. ; Zhu, Zhou ; Bochner, Bruce S. / Mice deficient in the St3gal3 gene product α2,3 sialyltransferase (ST3Gal-III) exhibit enhanced allergic eosinophilic airway inflammation. In: Journal of Allergy and Clinical Immunology. 2014 ; Vol. 133, No. 1.
@article{9e72ab7e66f14c608d3ab88c1b739ec5,
title = "Mice deficient in the St3gal3 gene product α2,3 sialyltransferase (ST3Gal-III) exhibit enhanced allergic eosinophilic airway inflammation",
abstract = "Background Sialic acid-binding immunoglobulin-like lectin (Siglec)-F is a proapoptotic receptor on mouse eosinophils, but little is known about its natural tissue ligand. Objective 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. Methods 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. Results 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 IgG 1 levels were increased in St3gal3-/- mice. Conclusions 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.",
keywords = "6′-sulfated sialyl Lewis X, 6′-sulfated sialyl N-acetyl-D-lactosamine, Eosinophils, Siglec-F, St3gal3, apoptosis, asthma, glycan ligands, lung",
author = "Takumi Kiwamoto and Brummet, {Mary E.} and Fan Wu and Motari, {Mary G.} and Smith, {David F.} and Schnaar, {Ronald L.} and Zhou Zhu and Bochner, {Bruce S.}",
year = "2014",
month = "1",
day = "1",
doi = "10.1016/j.jaci.2013.05.018",
language = "English (US)",
volume = "133",
journal = "Journal of Allergy and Clinical Immunology",
issn = "0091-6749",
publisher = "Mosby Inc.",
number = "1",

}

Mice deficient in the St3gal3 gene product α2,3 sialyltransferase (ST3Gal-III) exhibit enhanced allergic eosinophilic airway inflammation. / Kiwamoto, Takumi; Brummet, Mary E.; Wu, Fan; Motari, Mary G.; Smith, David F.; Schnaar, Ronald L.; Zhu, Zhou; Bochner, Bruce S.

In: Journal of Allergy and Clinical Immunology, Vol. 133, No. 1, 01.01.2014.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Mice deficient in the St3gal3 gene product α2,3 sialyltransferase (ST3Gal-III) exhibit enhanced allergic eosinophilic airway inflammation

AU - Kiwamoto, Takumi

AU - Brummet, Mary E.

AU - Wu, Fan

AU - Motari, Mary G.

AU - Smith, David F.

AU - Schnaar, Ronald L.

AU - Zhu, Zhou

AU - Bochner, Bruce S.

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Background Sialic acid-binding immunoglobulin-like lectin (Siglec)-F is a proapoptotic receptor on mouse eosinophils, but little is known about its natural tissue ligand. Objective 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. Methods 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. Results 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 IgG 1 levels were increased in St3gal3-/- mice. Conclusions 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.

AB - Background Sialic acid-binding immunoglobulin-like lectin (Siglec)-F is a proapoptotic receptor on mouse eosinophils, but little is known about its natural tissue ligand. Objective 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. Methods 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. Results 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 IgG 1 levels were increased in St3gal3-/- mice. Conclusions 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.

KW - 6′-sulfated sialyl Lewis X

KW - 6′-sulfated sialyl N-acetyl-D-lactosamine

KW - Eosinophils

KW - Siglec-F

KW - St3gal3

KW - apoptosis

KW - asthma

KW - glycan ligands

KW - lung

UR - http://www.scopus.com/inward/record.url?scp=84891738804&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84891738804&partnerID=8YFLogxK

U2 - 10.1016/j.jaci.2013.05.018

DO - 10.1016/j.jaci.2013.05.018

M3 - Article

VL - 133

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

SN - 0091-6749

IS - 1

ER -