Siglec-F-dependent negative regulation of allergen-induced eosinophilia depends critically on the experimental model

Immunol Lett. 2014 Jul;160(1):11-16. doi: 10.1016/j.imlet.2014.03.008. Epub 2014 Mar 31.

Abstract

Siglec-8 and siglec-F are paralogous membrane proteins expressed on human and murine eosinophils respectively. They bind similar sialylated and sulphated glycans and mediate eosinophil apoptosis when cross-linked with antibodies or glycan ligands. In models of allergic eosinophilic airway inflammation, siglec-F was shown previously to be important for negatively regulating eosinophilia. It was proposed that this was due to siglec-F-dependent apoptosis, triggered via engagement with ligands that are upregulated on bronchial epithelium. Our aim was to further investigate the functions of siglec-F by comparing two commonly used models of ovalbumin-induced airway inflammation that differ in the dose and route of administration of ovalbumin. In confirmation of published results, siglec-F-deficient mice had enhanced lung tissue eosinophilia in response to intranasal ovalbumin delivered every other day. However, following aerosolised ovalbumin delivered daily, there was no influence of siglec-F deficiency on lung eosinophilia. Expression of siglec-F ligands in lung tissues was similar in both models of allergen induced inflammation. These data demonstrate that siglec-F-dependent regulation of eosinophilia is subtle and depends critically on the model used. The findings also indicate that mechanisms other than ligand-induced apoptosis may be important in siglec-F-dependent suppression of eosinophilia.

Keywords: Allergic airway inflammation; Eosinophil; Siglec-8; Siglec-F.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allergens / immunology*
  • Animals
  • Antigens, Differentiation, Myelomonocytic / genetics
  • Antigens, Differentiation, Myelomonocytic / metabolism*
  • Disease Models, Animal
  • Eosinophilia / genetics
  • Eosinophilia / immunology*
  • Eosinophilia / metabolism*
  • Eosinophils / immunology
  • Eosinophils / metabolism
  • Female
  • Gene Order
  • Gene Targeting
  • Genetic Loci
  • Ligands
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Protein Binding
  • Respiratory Hypersensitivity / genetics
  • Respiratory Hypersensitivity / immunology
  • Respiratory Hypersensitivity / metabolism

Substances

  • Allergens
  • Antigens, Differentiation, Myelomonocytic
  • Ligands
  • Siglecf protein, mouse