Secretion of S100A8, S100A9, and S100A12 by Neutrophils Involves Reactive Oxygen Species and Potassium Efflux

S100A8/A9 (calprotectin) and S100A12 proinflammatory mediators are found at inflammatory sites and in the serum of patients with inflammatory or autoimmune diseases. These cytoplasmic proteins are secreted by neutrophils at sites of inflammation via alternative secretion pathways of which little is known. This study examined the nature of the stimuli leading to S100A8/A9 and S100A12 secretion as well as the mechanism involved in this alternative secretion pathway. Chemotactic agents, cytokines, and particulate molecules were used to stimulate human neutrophils. MSU crystals, PMA, and H2O2induced the release of S100A8, S100A9, and S100A12 homodimers, as well as S100A8/A9 heterodimer. High concentrations of S100A8/A9 and S100A12 were secreted in response to nanoparticles like MSU, silica, TiO2, fullerene, and single-wall carbon nanotubes as well as in response to microbe-derived molecules, such as zymosan or HKCA. However, neutrophils exposed to the chemotactic factors fMLP failed to secrete S100A8/A9 or S100A12. Secretion of S100A8/A9 was dependent on the production of reactive oxygen species and required K+exchanges through the ATP-sensitive K+channel. Altogether, these findings suggest that S100A12 and S100A8/A9 are secreted independently either via distinct mechanisms of secretion or following the activation of different signal transduction pathways.

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Environmentally persistent free radicals are ubiquitous in wildfire charcoals and remain stable for years

Communications Earth & Environment ◽

10.1038/s43247-021-00138-2 ◽

2021 ◽

Vol 2 (1) ◽

Author(s):

Gabriel Sigmund ◽

Cristina Santín ◽

Marc Pignitter ◽

Nathalie Tepe ◽

Stefan H. Doerr ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Free Radicals ◽

Reactive Oxygen ◽

Resonance Spectroscopy ◽

Oxygen Species ◽

Pyrogenic Carbon ◽

Spin Resonance ◽

Long Time ◽

High Concentrations

AbstractGlobally landscape fires produce about 256 Tg of pyrogenic carbon or charcoal each year. The role of charcoal as a source of environmentally persistent free radicals, which are precursors of potentially harmful reactive oxygen species, is poorly constrained. Here, we analyse 60 charcoal samples collected from 10 wildfires, that include crown as well as surface fires in forest, shrubland and grassland spanning different boreal, temperate, subtropical and tropical climate. Using electron spin resonance spectroscopy, we measure high concentrations of environmentally persistent free radicals in charcoal samples, much higher than those found in soils. Concentrations increased with degree of carbonization and woody fuels favoured higher concentrations. Moreover, environmentally persistent free radicals remained stable for an unexpectedly long time of at least 5 years. We suggest that wildfire charcoal is an important global source of environmentally persistent free radicals, and therefore potentially of harmful reactive oxygen species.

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Development, characterization and first deployment of an improved online reactive oxygen species analyzer

Atmospheric Measurement Techniques ◽

10.5194/amt-11-65-2018 ◽

2018 ◽

Vol 11 (1) ◽

pp. 65-80 ◽

Cited By ~ 12

Author(s):

Jun Zhou ◽

Emily A. Bruns ◽

Peter Zotter ◽

Giulia Stefenelli ◽

André S. H. Prévôt ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Detection Limit ◽

Atmospheric Aerosols ◽

Half Life ◽

Matrix Effects ◽

Reactive Oxygen ◽

Oxygen Species ◽

Wood Combustion ◽

Storage Duration ◽

High Concentrations

Abstract. Inhalation of atmospheric particles is linked to human diseases. Reactive oxygen species (ROS) present in these atmospheric aerosols may play an important role. However, the ROS content in aerosols and their formation pathways are still largely unknown. Here, we have developed an online and offline ROS analyzer using a 2′,7′-dichlorofluorescin (DCFH) based assay. The ROS analyzer was calibrated with H2O2 and its sensitivity was characterized using a suite of model organic compounds. The instrument detection limit determined as 3 times the noise is 1.3 nmol L−1 for offline analysis and 2 nmol m−3 of sampled air when the instrument is operated online at a fluorescence response time of approximately 8 min, while the offline method detection limit is 18 nmol L−1. Potential interferences from gas-phase O3 and NO2 as well as matrix effects of particulate SO42− and NO3− were tested, but not observed. Fe3+ had no influence on the ROS signal, while soluble Fe2+ reduced it if present at high concentrations in the extracts. Both online and offline methods were applied to identify the ROS content of different aerosol types, i.e., ambient aerosols as well as fresh and aged aerosols from wood combustion emissions. The stability of the ROS was assessed by comparing the ROS concentration measured by the same instrumentation online in situ with offline measurements. We also analyzed the evolution of ROS in specific samples by conducting the analysis after storage times of up to 4 months. The ROS were observed to decay with increasing storage duration. From their decay behavior, ROS in secondary organic aerosol (SOA) can be separated into short- and long-lived fractions. The half-life of the short-lived fraction was 1.7 ± 0.4 h, while the half-life of the long-lived fraction could not be determined with our uncertainties. All these measurements showed consistently that on average 60 ± 20 % of the ROS were very reactive and disappeared during the filter storage time. This demonstrates the importance of a fast online measurement of ROS.

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Helicobacter pylori water extracts prime human neutrophils for enhanced reactive oxygen species production and stimulate production of CXC chemokine but not CC chemokine

Gastroenterology ◽

10.1016/s0016-5085(08)83250-7 ◽

2001 ◽

Vol 120 (5) ◽

pp. A654

Author(s):

Tadashi Shimoyama ◽

Qiang Liu ◽

Shinsaku Fukuda ◽

Takashi Umeda ◽

Ichiro Mizuki ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Helicobacter Pylori ◽

Reactive Oxygen Species Production ◽

Reactive Oxygen ◽

Human Neutrophils ◽

Oxygen Species ◽

Water Extracts ◽

Cc Chemokine ◽

Cxc Chemokine ◽

Species Production

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Simultaneous use of electrochemistry and chemiluminescence to detect reactive oxygen species produced by human neutrophils

Cell Biology International ◽

10.1016/j.cellbi.2008.08.016 ◽

2008 ◽

Vol 32 (12) ◽

pp. 1486-1496 ◽

Cited By ~ 12

Author(s):

Sergey Shleev ◽

Jonas Wetterö ◽

Karl-Eric Magnusson ◽

Tautgirdas Ruzgas

Keyword(s):

Reactive Oxygen Species ◽

Reactive Oxygen ◽

Human Neutrophils ◽

Oxygen Species ◽

Simultaneous Use

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Role of Reactive Oxygen Species in Cancer Progression: Molecular Mechanisms and Recent Advancements

Biomolecules ◽

10.3390/biom9110735 ◽

2019 ◽

Vol 9 (11) ◽

pp. 735 ◽

Cited By ~ 79

Author(s):

Vaishali Aggarwal ◽

Hardeep Tuli ◽

Ayşegül Varol ◽

Falak Thakral ◽

Mukerrem Yerer ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Protein Kinase ◽

Cancer Cell ◽

Cancer Progression ◽

Molecular Mechanisms ◽

Reactive Oxygen ◽

Mitogen Activated Protein Kinase ◽

Oxygen Species ◽

Mitogen Activated Protein ◽

High Concentrations

Reactive oxygen species (ROS) play a pivotal role in biological processes and continuous ROS production in normal cells is controlled by the appropriate regulation between the silver lining of low and high ROS concentration mediated effects. Interestingly, ROS also dynamically influences the tumor microenvironment and is known to initiate cancer angiogenesis, metastasis, and survival at different concentrations. At moderate concentration, ROS activates the cancer cell survival signaling cascade involving mitogen-activated protein kinase/extracellular signal-regulated protein kinases 1/2 (MAPK/ERK1/2), p38, c-Jun N-terminal kinase (JNK), and phosphoinositide-3-kinase/ protein kinase B (PI3K/Akt), which in turn activate the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), matrix metalloproteinases (MMPs), and vascular endothelial growth factor (VEGF). At high concentrations, ROS can cause cancer cell apoptosis. Hence, it critically depends upon the ROS levels, to either augment tumorigenesis or lead to apoptosis. The major issue is targeting the dual actions of ROS effectively with respect to the concentration bias, which needs to be monitored carefully to impede tumor angiogenesis and metastasis for ROS to serve as potential therapeutic targets exogenously/endogenously. Overall, additional research is required to comprehend the potential of ROS as an effective anti-tumor modality and therapeutic target for treating malignancies.

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Involvement of Caspases in Neutrophil Apoptosis: Regulation by Reactive Oxygen Species

Blood ◽

10.1182/blood.v92.12.4808 ◽

1998 ◽

Vol 92 (12) ◽

pp. 4808-4818 ◽

Cited By ~ 236

Author(s):

Bengt Fadeel ◽

Anders Åhlin ◽

Jan-Inge Henter ◽

Sten Orrenius ◽

Mark B. Hampton

Keyword(s):

Reactive Oxygen Species ◽

Cell Death ◽

Nadph Oxidase ◽

Reactive Oxygen ◽

Human Neutrophils ◽

Neutrophil Apoptosis ◽

Dependent Manner ◽

Caspase Activity ◽

Oxygen Species ◽

Spontaneous Apoptosis

Abstract Human neutrophils have a short half-life and are believed to die by apoptosis or programmed cell death both in vivo and in vitro. We found that caspases are activated in a time-dependent manner in neutrophils undergoing spontaneous apoptosis, concomitant with other characteristic features of apoptotic cell death such as morphologic changes, phosphatidylserine (PS) exposure, and DNA fragmentation. The treatment of neutrophils with agonistic anti-Fas monoclonal antibodies (MoAbs) significantly accelerated this process. However, in cells treated with the potent neutrophil activator phorbol 12-myristate 13-acetate (PMA), caspase activity was only evident after pharmacologic inhibition of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Similarily, inhibition of the NADPH oxidase in constitutive and Fas/APO-1–triggered apoptosis resulted in increased rather than suppressed levels of caspase activity, suggesting that reactive oxygen species may prevent caspases from functioning optimally in these cells. Moreover, oxidants generated via the NADPH oxidase were essential for PS exposure during PMA-induced cell death, but not for neutrophils undergoing spontaneous apoptosis. We conclude that caspases are an important component of constitutive and Fas/APO-1–triggered neutrophil apoptosis. However, these redox sensitive enzymes are suppressed in activated neutrophils, and an alternate oxidant-dependent pathway is used to mediate PS exposure and neutrophil clearance under these conditions.

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