Eosinophil apoptosis is mediated by stimulators of cellular oxidative metabolisms and inhibited by antioxidants: involvement of a thiol-sensitive redox regulation in eosinophil cell death.
The mechanisms for induction of eosinophil apoptosis remain uncertain. The role of oxidative stress has not been investigated. The present study was undertaken to determine the role of reactive oxygen species (ROS) and selective antioxidants in eosinophil apoptosis. Eosinophils were cultured with sodium arsenite (SA) known to induce intracellular oxidative metabolites. There was a significant increase in the rate of eosinophil apoptosis with low concentrations of arsenite, whereas high concentrations showed rates of apoptosis similar to control medium. Investigating the role of intracellular oxidants by flow cytometry, we found that while inducing apoptosis, SA more than anti-Fas resulted in a significant dose-dependent production of intracellular H(2)O(2). In contrast, the extracellular release of superoxide decreased after stimulation with SA or anti-Fas as assessed by lucigenin-dependent chemiluminescence. Coincubation experiments demonstrated that arsenite-induced apoptosis can be nearly completely prevented by selective antioxidants such as glutathione (GSH) and N-acetyl-cysteine (NAC), but not dimethyl sulfoxide (DMSO) or taurine (TAUR). Moreover, GSH and NAC significantly reduced eosinophil apoptosis mediated by a monoclonal antibody directed to Fas antigen. Next it was shown that GSH and NAC, but not DMSO or TAUR, were able to significantly delay spontaneous apoptosis in unstimulated eosinophils. Taken together, these data point to an important role of oxygen-dependent mechanisms in the regulation of eosinophil survival and apoptosis. We propose that eosinophil apoptosis may be related to the ability of the cell to maintain an appropriate oxidant-antioxidant balance.
Wedi
B
B
Department of Dermatology, Hannover Medical University, Hannover, Germany.
Straede
J
J
Wieland
B
B
Kapp
A
A
D000111:Acetylcysteine / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology / Q000502:physiology; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D018053:Arsenites / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival; D002478:Cells, Cultured; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004804:Eosinophils / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D005978:Glutathione / Q000494:pharmacology; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D007700:Kinetics; D008163:Luminescent Measurements; D016877:Oxidants / Q000494:pharmacology*; D010084:Oxidation-Reduction; D017670:Sodium Compounds / Q000494:pharmacology; D013654:Taurine / Q000494:pharmacology; D019014:fas Receptor / Q000276:immunology / Q000502:physiology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000975:Antioxidants; D018053:Arsenites; D007377:Interleukin-3; D016877:Oxidants; D017670:Sodium Compounds; D019014:fas Receptor; D013654:Taurine; C017947:sodium arsenite; D005978:Glutathione; D000111:Acetylcysteine; D004121:Dimethyl Sulfoxide