Involvement of caspases and of mitochondria in Fas ligation‐induced eosinophil apoptosis: modulation by interleukin‐5 and interferon‐γ

In this study, we examined the relative importance of caspases and mitochondria in Fas- mediated eosinophil apoptosis. Stimulation of hu- man peripheral blood eosinophils with an agonistic anti-human Fas monoclonal antibody, but not with control IgM, induced a time-dependent increase in their apoptosis, which was associated with a loss in mitochondrial transmembrane potential (DC m) and with caspase-8 and caspase-3 activation. Inter- leukin (IL)-5 and interferon (IFN)-g, two cytokines known to prolong eosinophil survival, inhibited Fas-mediated apoptosis and caspase activation but poorly affected the decrease in DC m. Eosinophil incubation with bongkrekic acid, an inhibitor of the mitochondrial permeability transition pore (MPTP) opening, failed to modify Fas-mediated loss in DC m, caspase activation, and apoptosis. In contrast, caspase inhibitors markedly reduced eo- sinophil apoptosis without significantly affecting DC m dissipation. We conclude that caspase-8 and caspase-3 activation, but not MPTP opening, me- diate Fas-induced eosinophil apoptosis and are the main targets for the protective effect of IL-5 and IFN-g. J. Leukoc. Biol. 70: 767-775; 2001.