Fas deficiency delays the resolution of airway hyperresponsiveness after allergen sensitization and challenge.
see Reprint Collection.
J Allergy Clin Immunol 2001 Oct; 108(4):547-556.
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. CONCLUSION: These results suggest that Fas expression can regulate the onset and resolution of AHR through an increase in eosinophil apoptosis.
Duez, C; Tomkinson, A; Shultz, L D.; Bratton, D L.; and Gelfand, E W., " Fas deficiency delays the resolution of airway hyperresponsiveness after allergen sensitization and challenge." (2001). Faculty Research 2000 - 2009. 305.