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Intracellular neutrophil oxidants: From laboratory curiosity to clinical reality

Journal article
Authors Claes Dahlgren
Anna Karlsson
Johan Bylund
Published in Journal of Immunology
Volume 202
Issue 11
Pages 3127-3134
ISSN 0022-1767
Publication year 2019
Published at Institute of Medicine, Department of Rheumatology and Inflammation Research
Institute of Odontology, Section 3
Pages 3127-3134
Language en
Links dx.doi.org/10.4049/jimmunol.1900235
Keywords reduced nicotinamide adenine dinucleotide phosphate oxidase, cell compartmentalization, cell killing, cell membrane, chronic granulomatous disease, fluorometry, gene mutation, genetic code, human, inflammation, neutrophil, nonhuman, phagocyte, photometry, precipitation, priority journal, Review, signal transduction
Subject categories Clinical Medicine

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. © 2019 by The American Association of Immunologists, Inc.

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