Extra domain-A fibronectin is necessary for the development of nasal remodeling in chronic allergen-induced rhinitis

Ann Allergy Asthma Immunol. 2013 May;110(5):322-7. doi: 10.1016/j.anai.2013.03.002. Epub 2013 Mar 28.

Abstract

Background: Extra domain A-containing fibronectin (EDA-FN) is necessary for the development of allergen-induced lower airway fibrosis. The pathogenesis of fibrosis in allergic rhinitis has not been well studied.

Objectives: To determine whether EDA-fibronectin is necessary for the development of nasal remodeling in a murine model of chronic allergic rhinitis and in human allergic rhinitis.

Methods: EDA(-/-) and wild-type (WT) C57Bl/6 mice were sensitized intraperitoneally and then challenged with inhaled ovalbumin (OVA) or saline for 2 and 5 weeks. Clinical signs of rhinitis and histological analysis of nasal tissue were evaluated. Immunohistological staining for EDA-FN was performed in human tissue of inferior nasal conchae from patients with allergic rhinitis and controls.

Results: After 2 weeks of allergen exposure, only goblet cell hyperplasia and perivascular eosinophilia were observed. After 5 weeks, goblet cell number, thickening of the subepithelial layer, and extent and area of collagen deposition were increased in the nasal tissue of WT OVA (ovalbumin)-challenged mice as compared with saline controls (P < .0001, P < .0001, P = .018, and P = .03, respectively). Clinical signs of rhinitis were observed only in WT OVA-challenged mice. In the EDA(-/-) mice exposed to OVA, collagen deposition, collagen area, and subepithelial thickness showed no increase and were similar to saline control mice, whereas goblet cell hyperplasia was similar to WT OVA-challenged mice. EDA-FN expression was prominent in inferior conchae from patients with allergic rhinitis but was absent in control patients.

Conclusion: EDA-containing fibronectin is necessary for the development of nasal tissue fibrotic remodeling process in both murine and human allergic rhinitis.

MeSH terms

  • Adult
  • Allergens / immunology
  • Animals
  • Collagen / immunology
  • Eosinophilia / immunology
  • Female
  • Fibronectins / genetics
  • Fibronectins / immunology*
  • Goblet Cells / pathology
  • Humans
  • Hyperplasia / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Middle Aged
  • Nasal Mucosa / immunology*
  • Nasal Mucosa / pathology
  • Ovalbumin / immunology
  • Rhinitis / immunology*
  • Rhinitis / pathology

Substances

  • Allergens
  • Fibronectins
  • extra domain A fibronectin, human
  • extra domain A fibronectin, mouse
  • Ovalbumin
  • Collagen