scholarly journals Inhibition of the lymphocyte metabolic switch by the oxidative burst of human neutrophils

2015 ◽  
Vol 129 (6) ◽  
pp. 489-504 ◽  
Author(s):  
Philip A. Kramer ◽  
Lynn Prichard ◽  
Balu Chacko ◽  
Saranya Ravi ◽  
E. Turner Overton ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Nadph Oxidase ◽  
Oxidative Burst ◽  
Effector Function ◽  
Human Neutrophils ◽  
Glycolytic Metabolism ◽  
Metabolic Switch ◽  
Nadph Oxidase 2

The lymphocyte metabolic switch, a transition from a mitochondrial to a more glycolytic metabolism, is prevented by neutrophil-derived hydrogen peroxide (H2O2). We propose that NADPH oxidase-2 (NOX-2) mediates the neutrophil-dependent suppression of lymphocyte effector function.

Serotonin as a physiological substrate for myeloperoxidase and its superoxide-dependent oxidation to cytotoxic tryptamine-4,5-dione

2009 ◽  
Vol 425 (1) ◽  
pp. 285-293 ◽  
Author(s):  
Valdecir F. Ximenes ◽  
Ghassan J. Maghzal ◽  
Rufus Turner ◽  
Yoji Kato ◽  
Christine C. Winterbourn ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Nadph Oxidase ◽  
Tissue Damage ◽  
Acid Production ◽  
Hypochlorous Acid ◽  
Human Neutrophils ◽  
Toxic Metabolite ◽  
Inflammatory Processes ◽  
Physiological Substrates ◽  
Inflammatory Tissue

During inflammatory events, neutrophils and platelets interact to release a variety of mediators. Neutrophils generate superoxide and hydrogen peroxide, and also discharge the haem enzyme myeloperoxidase. Among numerous other mediators, platelets liberate serotonin (5-hydroxytryptamine), which is a classical neurotransmitter and vasoactive amine that has significant effects on inflammation and immunity. In the present study, we show that serotonin is a favoured substrate for myeloperoxidase because other physiological substrates for this enzyme, including chloride, did not affect its rate of oxidation. At low micromolar concentrations, serotonin enhanced hypochlorous acid production by both purified myeloperoxidase and neutrophils. At higher concentrations, it almost completely blocked the formation of hypochlorous acid. Serotonin was oxidized to a dimer by myeloperoxidase and hydrogen peroxide. It was also converted into tryptamine-4,5-dione, especially in the presence of superoxide. This toxic quinone was produced by stimulated neutrophils in a reaction that required myeloperoxidase. In plasma, stimulated human neutrophils oxidized serotonin to its dimer using the NADPH oxidase and myeloperoxidase. We propose that myeloperoxidase will oxidize serotonin at sites of inflammation. In doing so, it will impair its physiological functions and generate a toxic metabolite that will exacerbate inflammatory tissue damage. Consequently, oxidation of serotonin by myeloperoxidase may profoundly influence inflammatory processes.

Polyethylemine coated silver nanoparticles induce human neutrophils’ oxidative burst via NADPH oxidase, through the activation of PKC

2018 ◽  
Vol 295 ◽  
pp. S261
Author(s):  
T. Soares ◽  
M. Gónzalez-Gómez ◽  
J. Rivas ◽  
P. Freitas ◽  
F. Carvalho ◽  
...  
Keyword(s):  
Silver Nanoparticles ◽  
Nadph Oxidase ◽  
Oxidative Burst ◽  
Human Neutrophils

scholarly journals NADPH Oxidase 2 Derived Reactive Oxygen Species Promote CD8+ T cell Effector Function

2021 ◽  
Author(s):  
Jing Chen ◽  
Chao Liu ◽  
Anna V. Chernatynskaya ◽  
Brittney Newby ◽  
Todd M. Brusko ◽  
...  
Keyword(s):  
Transcription Factor ◽  
T Cell ◽  
Nadph Oxidase ◽  
Molecular Mechanisms ◽  
Cell Lineage ◽  
Lymphocyte Activation ◽  
Cell Receptor ◽  
Effector Function ◽  
Genetic Ablation ◽  
Nadph Oxidase 2

ABSTRACTOxidants participate in lymphocyte activation and function. We previously demonstrated that eliminating the activity of NADPH oxidase 2 (NOX2) significantly impaired the effectiveness of autoreactive CD8+ cytotoxic T lymphocytes (CTL). However, the molecular mechanisms impacting CTL function remain unknown. Here, we studied the role of NOX2 in both non-obese diabetic (NOD) mouse and human CTL function. Genetic ablation or chemical inhibition of NOX2 in CTL significantly suppressed activation-induced expression of the transcription factor T-bet, the master transcription factor of the Tc1 cell lineage, and T-bet target effectors genes such as IFNγ and granzyme B. Inhibition of NOX2 in both human and mouse CTL prevented target cell lysis. We identified that superoxide generated by NOX2 must be converted into hydrogen peroxide to transduce the redox signal in CTL. Further, we show that NOX2-generated oxidants deactivate the Tumor Suppressor Complex leading to mTOR complex 1 activation and CTL effector function. These results indicate that NOX2 plays a non-redundant role in T cell receptor-mediated CTL effector function.

scholarly journals The Macrolide Roxithromycin Impairs NADPH Oxidase Activation and Alters Translocation of Its Cytosolic Components to the Neutrophil Membrane In Vitro

2005 ◽  
Vol 49 (7) ◽  
pp. 2986-2989 ◽  
Author(s):  
Houria Abdelghaffar ◽  
Catherine Babin-Chevaye ◽  
Marie-Thérèse Labro
Keyword(s):  
Nadph Oxidase ◽  
Outer Membrane ◽  
Oxidative Burst ◽  
Active Enzyme ◽  
Human Neutrophils ◽  
Resting Cells ◽  
Enzymatic System ◽  
Oxidant Production ◽  
Nadph Oxidase Activation

ABSTRACT We have studied the interference of roxithromycin with NADPH oxidase, the key enzymatic system for oxidant production by human neutrophils. Roxithromycin alters the reconstitution of an active enzyme and impairs the translocation to the outer membrane of the cytosolic components p47-phox and p67-phox. Interestingly, in resting cells roxithromycin directly triggers the translocation of these factors without stimulating the oxidative burst.

Antioxidant activity from extra virgin olive oil via inhibition of hydrogen peroxide–mediated NADPH-oxidase 2 activation

Nutrition ◽  
2018 ◽  
Vol 55-56 ◽  
pp. 36-40 ◽  
Author(s):  
Roberto Carnevale ◽  
Cristina Nocella ◽  
Vittoria Cammisotto ◽  
Simona Bartimoccia ◽  
Roberto Monticolo ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Antioxidant Activity ◽  
Nadph Oxidase ◽  
Olive Oil ◽  
Virgin Olive Oil ◽  
Extra Virgin Olive Oil ◽  
Nadph Oxidase 2

scholarly journals Sex-dependent dysregulation of human neutrophil responses by bisphenol A

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Wioletta Ratajczak-Wrona ◽  
Marzena Garley ◽  
Malgorzata Rusak ◽  
Karolina Nowak ◽  
Jan Czerniecki ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Bisphenol A ◽  
Total Concentration ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Human Neutrophils ◽  
Boyden Chamber ◽  
No Production ◽  
Pathogen Elimination ◽  
Latex Beads

Abstract Background In the present study, we aimed to investigate selected functions of human neutrophils exposed to bisphenol A (BPA) under in vitro conditions. As BPA is classified among xenoestrogens, we compared its action and effects with those of 17β-estradiol (E2). Methods Chemotaxis of neutrophils was examined using the Boyden chamber. Their phagocytosis and nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) oxidase activity were assessed via Park’s method with latex beads and Park’s test with nitroblue tetrazolium. To assess the total concentration of nitric oxide (NO), the Griess reaction was utilized. Flow cytometry was used to assess the expression of cluster of differentiation (CD) antigens. The formation of neutrophil extracellular traps (NETs) was analyzed using a microscope (IN Cell Analyzer 2200 system). Expression of the investigated proteins was determined using Western blot. Results The analysis of results obtained for both sexes demonstrated that after exposure to BPA, the chemotactic capacity of neutrophils was reduced. In the presence of BPA, the phagocytic activity was found to be elevated in the cells obtained from women and reduced in the cells from men. Following exposure to BPA, the percentage of neutrophils with CD14 and CD284 (TLR4) expression, as well as the percentage of cells forming NETs, was increased in the cells from both sexes. The stimulatory role of BPA and E2 in the activation of NADPH oxidase was observed only in female cells. On the other hand, no influence of E2 on the expression of CD14 and CD284, chemotaxis, phagocytosis, and the amount of NET-positive neutrophils was found for both sexes. The study further showed that BPA intensified NO production and iNOS expression in the cells of both sexes. In addition, intensified expression of all tested PI3K-Akt pathway proteins was observed in male neutrophils. Conclusions The study demonstrated the influence of BPA on neutrophil functions associated with locomotion and pathogen elimination, which in turn may disturb the immune response of these cells in both women and men. Analysis of the obtained data showed that the effect of this xenoestrogen on the human neutrophils was more pronounced than E2.

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