From Flies to Men: ROS and the NADPH Oxidase in Phagocytes

Abstract

The cellular formation of reactive oxygen species (ROS) represents an evolutionary ancient antimicrobial defense system against microorganisms. The NADPH oxidases (NOX), which are predominantly localized to endosomes, and the electron transport chain in mitochondria are the major sources of ROS. Like any powerful immunological process, ROS formation has costs, in particular collateral tissue damage of the host. Moreover, microorganisms have developed defense mechanisms against ROS, an example for an arms race between species. Thus, although NOX orthologs have been identified in organisms as diverse as plants, fruit flies, rodents, and humans, ROS functions have developed and diversified to affect a multitude of cellular properties, i.e., far beyond direct antimicrobial activity. Here, we focus on the development of NOX in phagocytic cells, where the so-called respiratory burst in phagolysosomes contributes to the elimination of ingested microorganisms. Yet, NOX participates in cellular signaling in a cell-intrinsic and -extrinsic manner, e.g., via the release of ROS into the extracellular space. Accordingly, in humans, the inherited deficiency of NOX components is characterized by infections with bacteria and fungi and a seemingly independently dysregulated inflammatory response. Since ROS have both antimicrobial and immunomodulatory properties, their tight regulation in space and time is required for an efficient and well-balanced immune response, which allows for the reestablishment of tissue homeostasis. In addition, distinct NOX homologs expressed by non-phagocytic cells and mitochondrial ROS are interlinked with phagocytic NOX functions and thus affect the overall redox state of the tissue and the cellular activity in a complex fashion. Overall, the systematic and comparative analysis of cellular ROS functions in organisms of lower complexity provides clues for understanding the contribution of ROS and ROS deficiency to human health and disease.

Effects of Aqueous Dispersions of C60, C70 and Gd@C82 Fullerenes on Genes Involved in Oxidative Stress and Anti-Inflammatory Pathways

“…One of the primary sources of ROS in cells is NADPH oxidases (NOX), which are predominantly localized in endosomes [ 44 ]. We studied the expression of the NOX4 gene and protein in the cells following their incubation with AFDs of C 60 , C 70 , and Gd@C 82 .…”

miRNA‐146a Mimic Inhibits NOX4/P38 Signalling to Ameliorate Mouse Myocardial Ischaemia Reperfusion (I/R) Injury

“…During IR, ROS are mainly produced by the mitochondrial respiratory chain and NOx family enzymes. Other sources of ROS include xanthine oxidase (XO) and uncoupled nitric oxide synthase (NOS) [ 19 ]. To date, seven NOx subtypes (NOX1-5 and duox1-2) have been identified, among which NOX2 and NOX4 are the most abundantly expressed in the heart [ 20 ].…”

Effects of Aqueous Dispersions of C60, C70 and Gd@C82 Fullerenes on Genes Involved in Oxidative Stress and Anti-inflammatory Pathways

“…One of the primary sources of ROS in cells is NADPH oxidases (NOX), which are predominantly localized in endosomes [40]. We studied the expression of NOX4 gene and protein in the cells following their incubation with AFDs of C60, C70, and Gd@C82.…”