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Hypertonic Saline Suppresses NADPH Oxidase-Dependent Neutrophil Extracellular Trap Formation and Promotes Apoptosis

Overview of attention for article published in Frontiers in immunology, March 2018
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Title
Hypertonic Saline Suppresses NADPH Oxidase-Dependent Neutrophil Extracellular Trap Formation and Promotes Apoptosis
Published in
Frontiers in immunology, March 2018
DOI 10.3389/fimmu.2018.00359
Pubmed ID
Authors

Ajantha Nadesalingam, Jacky H. K. Chen, Armin Farahvash, Meraj A. Khan

Abstract

Tonicity of saline (NaCl) is important in regulating cellular functions and homeostasis. Hypertonic saline is administered to treat many inflammatory diseases, including cystic fibrosis. Excess neutrophil extracellular trap (NET) formation, or NETosis, is associated with many pathological conditions including chronic inflammation. Despite the known therapeutic benefits of hypertonic saline, its underlying mechanisms are not clearly understood. Therefore, we aimed to elucidate the effects of hypertonic saline in modulating NETosis. For this purpose, we purified human neutrophils and induced NETosis using agonists such as diacylglycerol mimetic phorbol myristate acetate (PMA), Gram-negative bacterial cell wall component lipopolysaccharide (LPS), calcium ionophores (A23187 and ionomycin fromStreptomyces conglobatus), and bacteria (Pseudomonas aeruginosaandStaphylococcus aureus). We then analyzed neutrophils and NETs using Sytox green assay, immunostaining of NET components and apoptosis markers, confocal microscopy, and pH sensing reagents. This study found that hypertonic NaCl suppresses nicotinamide adenine dinucleotide phosphate oxidase (NADPH2 or NOX2)-dependent NETosis induced by agonists PMA,Escherichia coliLPS (0111:B4 and O128:B12), andP. aeruginosa. Hypertonic saline also suppresses LPS- and PMA- induced reactive oxygen species production. It was determined that supplementing H2O2reverses the suppressive effect of hypertonic saline on NOX2-dependent NETosis. Many of the aforementioned suppressive effects were observed in the presence of equimolar concentrations of choline chloride and osmolytes (d-mannitol and d-sorbitol). This suggests that the mechanism by which hypertonic saline suppresses NOX2-dependent NETosis is via neutrophil dehydration. Hypertonic NaCl does not significantly alter the intracellular pH of neutrophils. We found that hypertonic NaCl induces apoptosis while suppressing NOX2-dependent NETosis. In contrast, hypertonic solutions do not suppress NOX2-independent NETosis. Although hypertonic saline partially suppresses ionomycin-induced NETosis, it enhances A23187-induced NETosis, and it does not alterS. aureus-induced NETosis. Overall, this study determined that hypertonic saline suppresses NOX2-dependent NETosis induced by several agonists; in contrast, it has variable effects on neutrophil death induced by NOX2-independent NETosis agonists. These findings are important in understanding the regulation of NETosis and apoptosis in neutrophils.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 62 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 62 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 10 16%
Student > Master 9 15%
Researcher 7 11%
Student > Bachelor 6 10%
Other 5 8%
Other 13 21%
Unknown 12 19%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 15 24%
Immunology and Microbiology 13 21%
Medicine and Dentistry 7 11%
Nursing and Health Professions 3 5%
Agricultural and Biological Sciences 3 5%
Other 7 11%
Unknown 14 23%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 30 March 2018.
All research outputs
#19,951,180
of 25,382,440 outputs
Outputs from Frontiers in immunology
#22,587
of 31,537 outputs
Outputs of similar age
#256,283
of 348,490 outputs
Outputs of similar age from Frontiers in immunology
#557
of 694 outputs
Altmetric has tracked 25,382,440 research outputs across all sources so far. This one is in the 18th percentile – i.e., 18% of other outputs scored the same or lower than it.
So far Altmetric has tracked 31,537 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.4. This one is in the 21st percentile – i.e., 21% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 348,490 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 21st percentile – i.e., 21% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 694 others from the same source and published within six weeks on either side of this one. This one is in the 14th percentile – i.e., 14% of its contemporaries scored the same or lower than it.