ACTIVATION OF THE FAS RECEPTOR ON LUNG EOSINOPHILS LEADS TO APOPTOSISAND THE RESOLUTION OF EOSINOPHILIC INFLAMMATION OF THE AIRWAYS

While considerable progress has been made in understanding the events by which eosinophils accumulate in various pathophysiological conditio ns, the mechanisms controlling the resolution of eosinophilic inflamma tion are poorly understood, In the present study, we demonstrate that lung eosinophils obtained by bronchoalveolar lavage (BAL) after aeroso l allergen provocation of immunized mice expressed the Fas receptor, S timulation of purified eosinophils in vitro with a monoclonal anti-Fas mAb (1 ng-l mu g/ml) induced a dose/time dependent loss of cell viabi lity from 24-72 h. Measurement of DNA fragmentation with propidium iod ide, confirmed that anti-Fas induced eosinophil death by apoptosis, Wh ile incubation with IL-3, IL-5, or GM-CSF prevented spontaneous apopto sis, these factors failed to prevent anti-Fas induced apoptosis, Admin istration of anti-Fas mAb to the lungs after the induction of a lung e osinophilia increased the number of peroxidase positive macrophages in BAL fluid 4-12 h later which was followed by a marked reduction in th e number of eosinophils in the airways, Importantly, Fas-mediated reso lution of eosinophilic inflammation occurred in the absence of any ove rt secondary inflammatory changes in the lungs. We speculate that defe cts in this pathway may at least in part explain the chronic eosinophi lic inflammation often observed in the lungs of asthmatic individuals.