Fas deficiency delays the resolution of airway hyperresponsiveness after allergen sensitization and challenge

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.

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).

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.

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.

These results suggest that Fas expression can regulate the onset and resolution of AHR through an increase in eosinophil apoptosis.