Neutrophil NET formation is regulated from the inside by myeloperoxidase-processed reactive oxygen species

Björnsdóttir, Halla; Welin, Amanda; Michaëlsson, Erik; Osla, Veronica; Berg, Stefan; Christenson, Karin; Sundqvist, Martina; Dahlgren, Cláes; Karlsson, Anna; Bylund, Johan

doi:10.1016/j.freeradbiomed.2015.10.398

Cited by 141 publications

(142 citation statements)

References 63 publications

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“…Preprocessing of ROS in the granules may first be required. 133 Granules and nuclear membranes are broken down, and cytolysis of the cell proceeds, with release of the NETs. These web-like structures trap circulating cells, and their associated constituents (histones, DNA, proteases, proteins) exert multiple proinflammatory and procoagulant effects, participating in the pathogenesis of both venous and arterial thrombosis.…”

Section: Neutrophil Extracellular Trapsmentioning

confidence: 99%

Cross Talk Pathways Between Coagulation and Inflammation

Foley

Conway

2016

Circulation Research

430

389

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Anatomic pathology studies performed over 150 years ago revealed that excessive activation of coagulation occurs in the setting of inflammation. However, it has taken over a century since these seminal observations were made to delineate the molecular mechanisms by which these systems interact and the extent to which they participate in the pathogenesis of multiple diseases. There is, in fact, extensive cross talk between coagulation and inflammation, whereby activation of one system may amplify activation of the other, a situation that, if unopposed, may result in tissue damage or even multiorgan failure. Characterizing the common triggers and pathways are key for the strategic design of effective therapeutic interventions. In this review, we highlight some of the key molecular interactions, some of which are already showing promise as therapeutic targets for inflammatory and thrombotic disorders. (Circ Res.

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Section: Neutrophil Extracellular Trapsmentioning

confidence: 99%

Cross Talk Pathways Between Coagulation and Inflammation

Foley

Conway

2016

Circulation Research

430

389

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“…1), may be due to enhanced neutrophil activation in these infected muscles. The heme enzyme MPO is a marker for activated neutrophils, and this enzyme is required for the production of antimicrobial oxidants in activated neutrophils (Klebanoff et al, 2013;Björnsdottir et al, 2015;Winterbourn et al, 2016). Twenty-four hours after surgery and P. aeruginosa infection, we evaluated the MPO protein levels of infected muscles or saline-treated uninfected muscles in animals treated with either 80 % or 30 % FiO 2 by Western immunobloting.…”

Section: Resultsmentioning

confidence: 99%

Perioperative high inspired oxygen fraction therapy reduces surgical site infection with Pseudomonas aeruginosa in rats

Goldufsky

Gupta

et al. 2016

Journal of Medical Microbiology

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Surgical site infection (SSI) remains one of the most important causes of healthcare-associated infections, accounting for~17 % of all hospital-acquired infections. Although short-term perioperative treatment with high fraction of inspired oxygen (FiO 2 ) has shown clinical benefits in reducing SSI in colorectal resection surgeries, the true clinical benefits of FiO 2 therapy in reducing SSI remain unclear because randomized controlled trials on this topic have yielded disparate results and inconsistent conclusions. To date, no animal study has been conducted to determine the efficacy of short-term perioperative treatments with high (FiO 2 >60 %) versus low (FiO 2 <40 %) oxygen in reducing SSI. In this report, we designed a rat model for muscle surgery to compare the effectiveness of short-term perioperative treatments with high (FiO 2 =80 %) versus a standard low (FiO 2 =30 %) oxygen in reducing SSI with Pseudomonas aeruginosaone of the most prevalent Gram-negative pathogens, responsible for nosocomial SSIs. Our data demonstrate that 5 h perioperative treatment with 80 % FiO 2 is significantly more effective in reducing SSI with P. aeruginosa compared to 30 % FiO 2 treatment. We further show that whilst 80 % FiO 2 treatment does not affect neutrophil infiltration into P. aeruginosa-infected muscles, neutrophils in the 80 % FiO 2 -treated and infected animal group are significantly more activated than neutrophils in the 30 % FiO 2 -treated and infected animal group, suggesting that high oxygen perioperative treatment reduces SSI with P. aeruginosa by enhancing neutrophil activation in infected wounds.

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“…NET formation is an effective mechanism employed by neutrophils to respond to infection, therefore, lack of NET formation has disease promoting implications. This phenomenon was observed with CGD patients; these patients do not have an operational (inactive) NADPH oxidase complex and suffer from recurrent infections (168,387).…”

Section: Discussionmentioning

confidence: 82%

“…Additionally, PMA induction of NETs usually occurs after 90 min of stimulation, but the ROS response happens within minutes, therefore a certain threshold level of ROS may be required for trigger of NETs (387). It has been reported that NETs may function to trap and kill microbes, or they may only be able to trap and the microbe evades the killing mechanism (149,151,386,388,389).…”

Section: Discussionmentioning

confidence: 99%

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Characterization of Filifactor alocis and its immune evasion strategies employed against human neutrophils.

Armstrong¹

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Neutrophil NET formation is regulated from the inside by myeloperoxidase-processed reactive oxygen species

Cited by 141 publications

References 63 publications

Cross Talk Pathways Between Coagulation and Inflammation

Cross Talk Pathways Between Coagulation and Inflammation

Perioperative high inspired oxygen fraction therapy reduces surgical site infection with Pseudomonas aeruginosa in rats

Characterization of Filifactor alocis and its immune evasion strategies employed against human neutrophils.

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