Intracellular Neutrophil Oxidants: From Laboratory Curiosity to Clinical Reality

The phagocyte NADPH oxidase is responsible for the neutrophil's great capacity to produce reactive oxygen species (ROS). The NADPH oxidase can be assembled in the plasma membrane, as well as in membranes of intracellular vesicles, giving neutrophils the ability to direct ROS production to distinct subcellular sites. Neutrophil ROS contribute to microbial killing, trigger formation of neutrophil extracellular traps and appear to partake in inflammation control. Consequently, function-disrupting mutations in the NADPH oxidase lead to chronic granulomatous disease, characterized by severe infections and inflammatory disorders. Recent experimental data and description of a novel chronic granulomatous disease subtype (p40^phox-deficiency) imply that ROS generated in intracellular compartments are key for NETosis and for controlling inflammatory signaling. We foresee boosted interest in intracellular ROS production. To fully understand where and how such ROS function, however, limitations of assay systems to measure ROS need to be appreciated, and the development of novel techniques/reagents would be highly useful.