Protection of human neutrophils against oxidative damage

This report reviews some of our work on the relative importance of the glutathione redox system and catalase in protecting human neutrophils in vitro against hydrogen peroxide, generated either by these cells during phagocytosis or artificially in the medium by an enzyme system.Neutrophils deficient in glutathione reductase were rapidly inactivated during phagocytosis, unless protected by scavengers of oxidative products in the medium. In contrast, normal neutrophils remained functionally active. Thus, despite the presence of a normal catalase activity, a defect in the glutathione system totally impairs the protection of neutrophils against their own metabolic products. In catalase-inhibited or catalase-deficient neutrophils, no damage was observed during phagocytosis. We conclude that the glutathione redox system is the most important protection system against damage by oxidative products of neutrophils.During incubation of neutrophils with glucose + glucose oxidase, an extracellular system that generates hydrogen peroxide, we found that both catalase and the glutathione redox system were needed for adequate protection against oxidative injury. Apparently, this extracellular stress cannot be efficiently dealth with by the glutathione system alone: co-operation with catalase is needed in this situation. Under certain conditions, oxidative damage was observed even when the level of reduced glutathione was still relatively high, indicating that perhaps catalase and glutathione each protect different cell structures, and that both systems are needed together for the preservation of the total cell function.