Involvement of a mitochondrial pathway and key role of hydrogen peroxide during eosinophil apoptosis induced by excretory-secretory products from Fasciola hepatica.
Eosinophils (Eo) are typically associated with immune response to helminth. Previously, we demonstrated that excretory-secretory products (ESP) from Fasciola hepatica induce eosinophil apoptosis by a caspase-dependent mechanism. In this study, we observed that ESP caused mitochondrial-membrane depolarization of eosinophils leading to the release of cytochrome c. Also, ESP induced an increase in the reactive oxygen species (ROS) production, which preceded the mitochondrial injury. We found a significant rise in hydrogen peroxide, but not in the anion superoxide levels. Furthermore, catalase, but not superoxide dismutase, inhibited the mitochondrial depolarization as well as apoptosis. So, ESP induce in Eo an early increase in the ROS production, mainly hydrogen peroxide, which precedes mitochondrial injury and leads again to apoptosis. Finally, we demonstrated the participation of hydrogen peroxide in the peritoneal Eo apoptosis in vivo, both during the early stages of experimental fasciolosis in rats and after intraperitoneal ESP treatment.
Serradell
Marianela C
MC
Centro de Investigaciones en Bioquímica Clínica e Inmunología, Consejo Nacional de Investigaciones Científicas y Técnicas, Departamento Bioquímica Clínica, Facultad Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
Guasconi
Lorena
L
Masih
Diana T
DT
D000818:Animals; D017209:Apoptosis; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D005210:Fasciola hepatica / Q000378:metabolism* / Q000472:pathogenicity; D005211:Fascioliasis / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007155:Immunologic Factors / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013481:Superoxides
D007155:Immunologic Factors; D017382:Reactive Oxygen Species; D013481:Superoxides; D006861:Hydrogen Peroxide; D019255:NADPH Oxidases