ROS production in phagocytes: why, when, and where?

Abstract

In the phagocytosis field, ROS production by the phagocyte NOX has been associated with pathogen killing for the last 50 years. Since the discovery of nonphagocyte NOX, numerous other roles for ROS production have been identified. Oxidative stress and ROS-mediated signaling have received much attention in recent years. Much lower concentrations of ROS may be required for signaling compared with microbial killing. Based on the discoveries in nonphagocytic cells, it became logical to look for ROS functions distinct from pathogen killing, even in phagocytes. ROS are now linked to various forms of cell death, to chemotaxis, and to numerous modifications of cellular processes, including the NOX itself. ROS functions are clearly concentration-dependent over a wide range of concentrations. How much is required for which function? Which species are required for how much time? Is ROS signaling only a side effect of bactericidal ROS production? One major obstacle to answer these questions is the difficulty of reliable quantitative ROS detection. Signal transduction often takes place on a subcellular scale over periods of seconds or minutes, so the detection methods need to provide appropriate time and space resolution. We present examples of local ROS production, decreased degradation, signaling events, and potentially ROS-sensitive functions. We attempt to illustrate the current limitations for quantitative spatiotemporal ROS detection and point out directions for ongoing development. Probes for localized ROS detection and for combined detection of ROS, together with protein localization or other cellular parameters, are constantly improved.

Integrated High-Content Quantification of Intracellular ROS Levels and Mitochondrial Morphofunction

“…during normal cellular respiration in mitochondria (Babior 1999;Turrens 2003;Murphy 2009). The NOX family of NADPH oxidases (NOX1, NOX2, NOX3, NOX4, NOX5, DUOX1 and DUOX2) are proteins that transport electrons (e -) from NADPH across biological membranes (plasma or endomembranes) (Bedard and Krause 2007;Dupre-Crochet et al 2013). The activation mechanisms and tissue distribution of the isoforms differ but they all use O 2 as e --acceptor, producing O 2…”

Characterization of Filifactor alocis and its immune evasion strategies employed against human neutrophils.

“…It has been implicated that bacterial survival is dependent on manipulating neutrophils ability to perform phagocytosis and induce an ROS response (127). As neutrophils effectively employ their respiratory burst response upon challenge with numerous bacterial and fungal pathogens, these pathogens must utilize their stress response mechanisms to ensure avoidance or evasion of the neutrophil, leading to their persistence and survival (326). It is known that neutrophils are efficiently recruited and found in the oral cavity, therefore the studies into the killing mechanisms at this site are important to determine in the context of F. alocis infection and further periodontal disease.…”

“…After internalization by neutrophils, Staphylococcus aureus upregulates agr virulence genes which allows for it to survive inside the neutrophil, potentially through the use of membrane lytic toxins (326,327). Catalase aids S. aureus survival by protecting the bacterium once it has been internalized, through the conversion of hydrogen peroxide to oxygen and water (328,329).…”

O extrato etanólico das folhas de Baccharis dracunculifolia (Asteraceae) modula funções efetoras de neutrófilos: um promissor agente fitoterápico para o tratamento de processos inflamatórios mediados por estas células

“…Este método permite uma boa avaliação da cinética do metabolismo oxidativo dos PMNs, possibilitando o monitoramento do início, da amplitude e também do fim da produção das ERO (Dupre-Crochet et al, 2013). Além disso, como a produção de QL é dependente de ERO, este método tem sido empregado no estudo de substâncias com atividade antioxidante, sendo muito utilizado para a verificação da atividade antioxidante de produtos naturais em PMNs (Zielinska et al, 2000;Kanashiro et al, 2007;Simões-Ambrosio et al, 2010;Andrade et al, 2013;Czerwińska et al, 2013;Vongsak et al, 2013;Fernandes et al, 2014;Santos et al, 2014).…”

“…A importância das ERO na defesa do organismo fica bastante evidente pela grande susceptibilidade às infecções de indivíduos com Doença Granulomatosa Crônica (DGC, uma doença genética em que a NADPH oxidase é inativa ou tem sua atividade fortemente reduzida), em que os pacientes necessitam constantemente de terapia com antibióticos ou antifúngicos para combater os micro-organismos Bardoel et al, 2014 (Smith;Weidemann, 1993;Freitas et al, 2009;Dupre-Crochet et al, 2013).…”