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

Nadesalingam, Ajantha; Chen, Jacky; Farahvash, Armin; Khan, Meraj A.

doi:10.3389/fimmu.2018.00359

Cited by 48 publications

(47 citation statements)

References 77 publications

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“…Therefore, we wanted to determine whether the HS-increased antibacterial effects observed here similarly hinge on enhanced NO and/or ROS (reactive oxygen species) production. In line with a recent publication [33], HS treatment decreased ROS production in E. coliinfected MΦ (Figure 3(a)). In MΦ from mice deficient for the Cybb (cytochrome b 245 subunit of phagocyte NADPH oxidase [cybb -/-]), HS treatment similarly increased antibacterial activity (Figure 3(b)).…”

Section: Increased Antibacterial Activity Of Macrophages Under High Nsupporting

confidence: 92%

HIF1A and NFAT5 coordinate Na⁺-boosted antibacterial defense via enhanced autophagy and autolysosomal targeting

et al. 2019

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Infection and inflammation are able to induce diet-independent Na +-accumulation without commensurate water retention in afflicted tissues, which favors the pro-inflammatory activation of mouse macrophages and augments their antibacterial and antiparasitic activity. While Na +-boosted host defense against the protozoan parasite Leishmania major is mediated by increased expression of the leishmanicidal NOS2 (nitric oxide synthase 2, inducible), the molecular mechanisms underpinning this enhanced antibacterial defense of mouse macrophages with high Na + (HS) exposure are unknown. Here, we provide evidence that HS-increased antibacterial activity against E. coli was neither dependent on NOS2 nor on the phagocyte oxidase. In contrast, HS-augmented antibacterial defense hinged on HIF1A (hypoxia inducible factor 1, alpha subunit)-dependent increased autophagy, and NFAT5 (nuclear factor of activated T cells 5)-dependent targeting of intracellular E. coli to acidic autolysosomal compartments. Overall, these findings suggest that the autolysosomal compartment is a novel target of Na +modulated cell autonomous innate immunity.

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Section: Increased Antibacterial Activity Of Macrophages Under High Nsupporting

confidence: 92%

HIF1A and NFAT5 coordinate Na⁺-boosted antibacterial defense via enhanced autophagy and autolysosomal targeting

et al. 2019

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“…Given the important role NETosis plays in CF inflammation, drugs that inhibit NETosis or inhibit the interaction of NETs with other immune cells and epithelial cells may have a significant impact on CF airway inflammation. Such speculation has been confirmed in recent laboratory studies that demonstrated that hypertonic saline suppressed NETosis and reactive oxygen species production induced by exposure to LPS, P aeruginosa and other triggers …”

Section: Cellular Contributions To the Cf Airway Inflammatory Responsementioning

confidence: 83%

“…Such speculation has been confirmed in recent laboratory studies that demonstrated that S36 | hypertonic saline suppressed NETosis and reactive oxygen species production induced by exposure to LPS, P aeruginosa and other triggers. 74…”

Section: Neutrophilsmentioning

confidence: 99%

Inflammation in cystic fibrosis: An update

Roesch

Nichols

Chmiel

2018

Pediatric Pulmonology

203

221

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Inflammation plays a critical role in cystic fibrosis (CF) lung pathology and disease progression making it an active area of research and important therapeutic target. In this review, we explore the most recent research on the major contributors to the exuberant inflammatory response seen in CF as well as potential therapeutics to combat this response. Absence of functional cystic fibrosis transmembrane conductance regulator (CFTR) alters anion transport across CF airway epithelial cells and ultimately results in dehydration of the airway surface liquid. The dehydrated airway surface liquid in combination with abnormal mucin secretion contributes to airway obstruction and subsequent infection that may serve as a trigger point for inflammation. There is also evidence to suggest that airway inflammation may be excessive and sustained relative to the infectious stimuli. Studies have shown dysregulation of both pro-inflammatory mediators such as IL-17 and pro-resolution mediators including metabolites of the eicosanoid pathway. Recently, CFTR potentiators and correctors have garnered much attention in the CF community. Although these modulators address the underlying defect in CF, their impact on downstream consequences such as inflammation are not known. Here, we review pre-clinical and clinical data on the impact of CFTR modulators on inflammation. In addition, we examine other cell types including neutrophils, macrophages, and T-lymphocytes that express CFTR and contribute to the CF inflammatory response. Finally, we address challenges in developing anti-inflammatory therapies and highlight some of the most promising anti-inflammatory drugs under development for CF.

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“…Also, no real consensus yet exists about which medium to use for the storage of neutrophils prior to or during assessing NET formation in vitro, although the composition of the culture medium strongly influences the propensity to form NETs [153,154] (st. 80). Also, NET assays must be performed under controlled CO 2 /HCO 3 -/pH balance [155][156][157] (st. 81).…”

Section: Materials and Methods In Net-related Researchmentioning

confidence: 99%

To NET or not to NET:current opinions and state of the science regarding the formation of neutrophil extracellular traps

et al. 2019

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Since the discovery and definition of neutrophil extracellular traps (NETs) 14 years ago, numerous characteristics and physiological functions of NETs have been uncovered. Nowadays, the field continues to expand and novel mechanisms that orchestrate formation of NETs, their previously unknown properties, and novel implications in disease continue to emerge. The abundance of available data has also led to some confusion in the NET research community due to contradictory results and divergent scientific concepts, such as pro-and anti-inflammatory roles in pathologic conditions, demarcation from other forms of cell death, or the origin of the DNA that forms the NET scaffold. Here, we present prevailing concepts and state of the science in NET-related research and elaborate on open questions and areas of dispute.

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

Cited by 48 publications

References 77 publications

HIF1A and NFAT5 coordinate Na⁺-boosted antibacterial defense via enhanced autophagy and autolysosomal targeting

HIF1A and NFAT5 coordinate Na⁺-boosted antibacterial defense via enhanced autophagy and autolysosomal targeting

Inflammation in cystic fibrosis: An update

To NET or not to NET:current opinions and state of the science regarding the formation of neutrophil extracellular traps

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

Cited by 48 publications

References 77 publications

HIF1A and NFAT5 coordinate Na+-boosted antibacterial defense via enhanced autophagy and autolysosomal targeting

HIF1A and NFAT5 coordinate Na+-boosted antibacterial defense via enhanced autophagy and autolysosomal targeting

Inflammation in cystic fibrosis: An update

To NET or not to NET:current opinions and state of the science regarding the formation of neutrophil extracellular traps

Contact Info

Product

Resources

About

HIF1A and NFAT5 coordinate Na⁺-boosted antibacterial defense via enhanced autophagy and autolysosomal targeting

HIF1A and NFAT5 coordinate Na⁺-boosted antibacterial defense via enhanced autophagy and autolysosomal targeting