Intracellular Neutrophil Oxidants: From Laboratory Curiosity to Clinical Reality
- 1 June 2019
- journal article
- review article
- Published by The American Association of Immunologists in The Journal of Immunology
- Vol. 202 (11), 3127-3134
- https://doi.org/10.4049/jimmunol.1900235
Abstract
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 (p40phox-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.Keywords
This publication has 85 references indexed in Scilit:
- How does the oxidative burst of macrophages kill bacteria? Still an open questionMolecular Microbiology, 2011
- Chronic Granulomatous Disease: Lessons from a Rare DisorderTransplantation and Cellular Therapy, 2011
- Residual NADPH Oxidase and Survival in Chronic Granulomatous DiseaseThe New England Journal of Medicine, 2010
- Inflammasome activation in NADPH oxidase defective mononuclear phagocytes from patients with chronic granulomatous diseaseBlood, 2010
- Reactive oxygen species–independent activation of the IL-1β inflammasome in cells from patients with chronic granulomatous diseaseProceedings of the National Academy of Sciences of the United States of America, 2010
- Reactive oxygen species in phagocytic leukocytesHistochemistry and Cell Biology, 2008
- Inflammatory Manifestations in Chronic Granulomatous Disease (CGD)Journal of Clinical Immunology, 2008
- Novel cell death program leads to neutrophil extracellular trapsThe Journal of cell biology, 2007
- Neutrophils from p40phox−/− mice exhibit severe defects in NADPH oxidase regulation and oxidant-dependent bacterial killingThe Journal of Experimental Medicine, 2006
- Neutrophil Extracellular Traps Kill BacteriaScience, 2004