Role of extracellular superoxide in neutrophil activation: interactions between xanthine oxidase and TLR4 induce proinflammatory cytokine production

Lorne, Emmanuel; Żmijewski, Jaroslaw W.; Zhao, Xia; Liu, Gang; Tsuruta, Yuko; Park, Young-Jun; Dupont, Hervé; Abraham, Edward

doi:10.1152/ajpcell.00454.2007

Cited by 75 publications

(71 citation statements)

References 45 publications

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“…(46) The association of TLR-4 with xanthine oxidase was previously shown to result in neutrophil activation by superoxide. (25) In our study, we found that superoxideinduced NET formation does not occur in TLR-4 KO neutrophils. Our finding builds upon the previous discovery that oxidants enhance TLR-4 signaling in innate immune cells, specifically macrophages.…”

Section: Disclosurementioning

confidence: 42%

“…To determine the NET-inducing effect on neutrophils, we utilized xanthine oxidase and its substrate hypoxanthine to generate superoxide. (25) When neutrophils form NETs, decondensed chromatin studded with various proteins is expelled to form distinctive extracellular web-like structures. (3,4) We visualized this process by immunofluorescence after treatment of purified neutrophils in culture with superoxide.…”

Section: Superoxide Induces Neutrophil Extracellular Trapsmentioning

confidence: 99%

“…Neutrophils express most Toll-like receptors (TLRs), and their activation has been reported to induce NETs in response to recognized neutrophil stimuli, such as LPS, (3) (25) revealed that neutrophil TLR-4 interaction with superoxide triggers neutrophil activation, promotion of NF-κB effects and production of proinflammatory cytokines. We sought to establish whether NET formation to superoxide occurs through TLR-4 activation.…”

Section: Net Formation By Superoxide Requires Toll-like Receptormentioning

confidence: 99%

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Superoxide induces Neutrophil Extracellular Trap Formation in a TLR-4 and NOX-Dependent Mechanism

Al-Khafaji

Tohme

Yazdani

et al. 2016

Mol Med

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Neutrophils constitute the early innate immune response to perceived infectious and sterile threats. Neutrophil extracellular traps (NETs) are a novel mechanism to counter pathogenic invasion and sequelae of ischemia, including cell death and oxidative stress. Superoxide is a radical intermediate of oxygen metabolism produced by parenchymal and nonparenchymal hepatic cells, and is a hallmark of oxidative stress after liver ischemia-reperfusion (I/R). While extracellular superoxide recruits neutrophils to the liver and initiates sterile inflammatory injury, it is unknown whether superoxide induces the formation of NETs. We hypothesize that superoxide induces NET formation through a signaling cascade involving Toll-like receptor 4 (TLR-4) and neutrophil NADPH oxidase (NOX). We treated neutrophils with extracellular superoxide and observed NET DNA release, histone H3 citrullination and increased levels of MPO-DNA complexes occurring in a TLR-4-dependent manner. Inhibition of superoxide generation by allopurinol and inhibition of NOX by diphenyleneiodonium prevented NET formation. When mice were subjected to warm liver I/R, we found significant NET formation associated with liver necrosis and increased serum ALT in TLR-4 WT but not TLR-4 KO mice. To reduce circulating superoxide, we pretreated mice undergoing I/R with allopurinol and N-acetylcysteine, which resulted in decreased NETs and ameliorated liver injury. Our study demonstrates a requirement for TLR-4 and NOX in superoxide-induced NETs, and suggests involvement of superoxide-induced NETs in pathophysiologic settings.

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Section: Disclosurementioning

confidence: 42%

Section: Superoxide Induces Neutrophil Extracellular Trapsmentioning

confidence: 99%

Section: Net Formation By Superoxide Requires Toll-like Receptormentioning

confidence: 99%

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Superoxide induces Neutrophil Extracellular Trap Formation in a TLR-4 and NOX-Dependent Mechanism

Al-Khafaji

Tohme

Yazdani

et al. 2016

Mol Med

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“…However, recent data suggest that different ROS may have distinct effects on cellular activation. For example, whereas exposure to superoxide appears to increase the release of proinflammatory mediators, such as cytokines, by neutrophils and other cellular populations, elevated intracellular concentrations of H 2 O 2 diminish LPS-induced neutrophil activation (6)(7)(8)(9).…”

mentioning

confidence: 99%

Antiinflammatory Effects of Hydrogen Peroxide in Neutrophil Activation and Acute Lung Injury

Żmijewski¹,

Lorne²,

Zhao³

et al. 2009

Am J Respir Crit Care Med

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Rationale: Although reactive oxygen species (ROS) are generally considered to be proinflammatory and to contribute to cellular and organ dysfunction when present in excessive amounts, there is evidence that specific ROS, particularly hydrogen peroxide (H 2 O 2 ), may have antiinflammatory properties. Objectives: To address the role that increases in intracellular H 2 O 2 may play in acute inflammatory processes, we examined the effects of catalase inhibition or the absence of catalase on LPS-induced inflammatory responses. Methods: Neutrophils from control or acatalasemic mice, or control neutrophils incubated with the catalase inhibitor aminotriazole, were treated with LPS, and levels of reactive oxygen species, proteasomal activity, NF-kB activation, and proinflammatory cytokine expression were measured. Acute lung injury (ALI) was produced by intratracheal injection of LPS into control, acatalasemic-, or aminotriazole-treated mice. Measurements and Main Results: Intracellular levels of H 2 O 2 were increased in acatalasemic neutrophils and in neutrophils exposed to aminotriazole. Compared with LPS-stimulated neutrophils from control mice, neutrophils from acatalasemic mice or neutrophils treated with aminotriazole demonstrated reduced 20S and 26S proteasomal activity, IkB-a degradation, NF-kB nuclear accumulation, and production of the proinflammatory cytokines TNF-a and macrophage inhibitory protein (MIP)-2. The severity of LPS-induced ALI was less in acatalasemic mice and in mice treated with aminotriazole as compared with that found in control mice. Conclusions: These results indicate that H 2 O 2 has antiinflammatory effects on neutrophil activation and inflammatory processes, such as ALI, in which activated neutrophils play a major role.

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“…Evidence concerning that TLR plays important roles in cardiovascular pathologies such as especially myocardial IR and atherosclerosis is getting increased [21]. It has been demonstrated that extracellular O 2 -which develops due to Xantine oxidase in IR injury activates neutrophils and induced neutrophil-related proinflammatory response occurs via TLR-4-related mechanisms [22]. In a study conducted with mice, high level of TLR-4 expression was determined in ventricular muscle 4 days after MI and it was reported that protection against myocardial inflammatory injury occurs in TLR-4 knock-out mice [23].…”

Section: Discussionmentioning

confidence: 99%

Effects of At2 Receptor Agonist Novokinin on Oxidative Stress, Inflammation and Infarct Size Due to Myocardial Ischemia-Reperfusion

E¹,

Şahna²

2017

JBiSE

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Aim: Ischemia and reperfusion (IR) injury is a serious problem that is occurred during thrombolytic therapy, organ transplantation, coronary angioplasty, and cardiopulmonary bypass. There is an increase in the number of AT2 receptors in some pathological conditions such as cardiac hypertrophy, myocardial infarction, congestive heart failure. This study was designed to investigate the effects AT2 receptor agonist Novokinin on infarct size, caveolin-1 (CAV-1), HSP90, ADMA, NADPH oxidase and Rhokinase associated to endothelial dysfunction and oxidative stress, and NFκB and TLR-4 levels induced by inflammation on myocardial IR. Methods: The experimental groups: Sham (C), Novokinin (N), IR and IRN. Novokinin was performed with infusion pump before ischemia, and during IR. The left main coronary artery was occluded for 30 minutes ischemia followed by 120 minutes reperfusion in anesthetized rats. CAV-1, HSP90, and NFκB levels were measured by the quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), ADMA, TLR-4, NADPH oxidase, and Rhokinase levels were measured by ELISA, infarct size was measured by ImageJ, an image analysis software, in the heart tissue. Results: NFκB, HSP90, NADPH oxidase and TLR-4 levels increased with IR and significantly decreased with Novokinin. CAV-1 levels were not different between the groups. ADMA and Rhokinase levels were increased due to IR but decreased with Novokinin. Novokinin reduced infarct size due to IR. Conclusion: Our results showed that, ADMA, HSP90, NFκB, TLR-4, Rhokinase, and NADPH oxidase levels play important roles on IR injury. AT2 receptor agonist Novokinin may affect positively oxidative changes, inflammation, and endothelial function in myocardial IR injury.

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Role of extracellular superoxide in neutrophil activation: interactions between xanthine oxidase and TLR4 induce proinflammatory cytokine production

Cited by 75 publications

References 45 publications

Superoxide induces Neutrophil Extracellular Trap Formation in a TLR-4 and NOX-Dependent Mechanism

Superoxide induces Neutrophil Extracellular Trap Formation in a TLR-4 and NOX-Dependent Mechanism

Antiinflammatory Effects of Hydrogen Peroxide in Neutrophil Activation and Acute Lung Injury

Effects of At2 Receptor Agonist Novokinin on Oxidative Stress, Inflammation and Infarct Size Due to Myocardial Ischemia-Reperfusion

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