title: Fas deficiency delays the resolution of airway hyperresponsiveness after allergen sensitization and challenge.
abstract: BACKGROUND
  In asthma, persistent inflammation might be the result of (1) an impaired ability to clear inflammatory cells from the airways and/or (2) impaired apoptotic responses.
  
  
  OBJECTIVE
  In a mouse model, we investigated the regulatory role of Fas (CD95)-induced apoptosis in the development and resolution of airway inflammation and airway hyperresponsiveness (AHR).
  
  
  METHODS
  Mice that were either Fas-sufficient (wild-type; WT) or Fas-deficient (lpr ) were sensitized by intraperitoneal injections of ovalbumin (OVA) and challenged once intranasally with OVA (IP-IN mice). Control (IN) mice were challenged only.
  
  
  RESULTS
  IP-IN WT mice developed AHR at 48 hours; changes in airway resistance resolved by 96 hours. Airway responsiveness at 48 hours in IP-IN lpr mice was similar to that in IP-IN WT mice. However, in contrast to WT mice, IP-IN lpr mice sustained significant AHR at 96 hours in comparison with IN lpr mice; the AHR resolved by 6 days. Bronchoalveolar lavage fluid cell composition was similar in all of the different groups at 48 hours and 96 hours. Both IP-IN WT mice and lpr mice exhibited similar tissue eosinophilia, whereas IP-IN lpr mice had significantly lower numbers of TdT-mediated dUTP nick end labeling (TUNEL)-positive cells in comparison with IP-IN WT mice at 48 hours. Anti-IL-5 antibody given to IP-IN lpr mice 48 hours and 72 hours after the challenge significantly decreased AHR and eosinophilic inflammation and increased TUNEL-positive cell numbers at 96 hours.
  
  
  CONCLUSIONS
  These results suggest that Fas expression can regulate the onset and resolution of AHR through an increase in eosinophil apoptosis.
authors.affiliation: Division of Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, Denver; and the Jackson Laboratory, Bar Harbor.
authors.forename: C
authors.initials: C
authors.lastname: Duez
authors.forename: A
authors.initials: A
authors.lastname: Tomkinson
authors.forename: L D
authors.initials: LD
authors.lastname: Shultz
authors.forename: D L
authors.initials: DL
authors.lastname: Bratton
authors.forename: E W
authors.initials: EW
authors.lastname: Gelfand
mesh_terms: D000485:Allergens / Q000276:immunology*; D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D015848:Interleukin-5 / Q000276:immunology; D008232:Lymphoproliferative Disorders / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D009299:Nasal Provocation Tests; D010047:Ovalbumin / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000209:etiology / Q000276:immunology*; D019014:fas Receptor / Q000235:genetics / Q000276:immunology*
chemical_list: D000485:Allergens; D015848:Interleukin-5; D019014:fas Receptor; D010047:Ovalbumin