title: Development of a mouse model for chronic cat allergen-induced asthma.
abstract: BACKGROUND
  Allergic asthma is a chronic inflammatory airway disease caused by exposure to airborne allergens. In order to develop novel therapies for allergic asthma, models that are relevant to human disease are needed.
  
  
  METHODS
  Female BALB/c mice were presensitised subcutaneously with alum-adsorbed recombinant cat allergen Fel d 1, followed by intranasal challenges with cat dander extract spiked with recombinant Fel d 1 for 7 weeks. For reference, mice were presensitised and challenged with ovalbumin following the same protocol. Airway hyperresponsiveness, serum antibodies, airway inflammation and cell infiltration, and cytokines in lung tissue and bronchoalveolar lavage were measured.
  
  
  RESULTS
  Mice presensitised with recombinant Fel d 1 and challenged with cat dander extract or presensitised and challenged with ovalbumin showed airway hyperresponsiveness in response to metacholine. Mice of the cat allergen model showed influx of neutrophils, eosinophils and lymphocytes in bronchoalveolar lavage, combined with increased levels of IL-17a and increased IL-4 mRNA expression in lung tissue. In contrast, mice sensitised and challenged with ovalbumin showed a predominant influx of eosinophils in bronchoalveolar lavage and had an increased expression of IL-5 in lung tissue. Both protocols induced features of lung tissue remodelling and allergen-specific antibody responses.
  
  
  CONCLUSIONS
  The presented mouse model for cat allergen-induced asthma exhibits hallmarks of chronic allergic asthma, like airway hyperresponsiveness, a mixed neutrophilic/eosinophilic infiltration in bronchoalveolar lavage, expression of IL-17a and signs of remodelling in lung tissue. The model will provide a relevant platform for the development of novel treatment strategies.
authors.affiliation: Clinical Immunology and Allergy Unit, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Jeanette
authors.initials: J
authors.lastname: Grundström
authors.forename: Tiiu
authors.initials: T
authors.lastname: Saarne
authors.forename: Cecilia
authors.initials: C
authors.lastname: Kemi
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Gregory
authors.forename: Konrad
authors.initials: K
authors.lastname: Wadén
authors.forename: Marina C
authors.initials: MC
authors.lastname: Pils
authors.forename: Mikael
authors.initials: M
authors.lastname: Adner
authors.forename: Guro
authors.initials: G
authors.lastname: Gafvelin
authors.forename: Marianne
authors.initials: M
authors.lastname: van Hage
mesh_terms: D056151:Airway Remodeling; D000818:Animals; D000906:Antibodies / Q000097:blood; D001249:Asthma / Q000276:immunology*; D016535:Bronchial Hyperreactivity; D002415:Cats; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D063607:Dander / Q000276:immunology; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology*; D005260:Female; D006023:Glycoproteins / Q000276:immunology; D006801:Humans; D007114:Immunization; D008214:Lymphocytes / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology
chemical_list: D000906:Antibodies; D016207:Cytokines; D006023:Glycoproteins; D011994:Recombinant Proteins; C059296:Fel d 1 protein, Felis domesticus