scholarly journals Neutrophil Extracellular Traps Induce Organ Damage during Experimental and Clinical Sepsis

PLoS ONE ◽  
2016 ◽  
Vol 11 (2) ◽  
pp. e0148142 ◽  
Author(s):  
Paula Giselle Czaikoski ◽  
José Maurício Segundo Correia Mota ◽  
Daniele Carvalho Nascimento ◽  
Fabiane Sônego ◽  
Fernanda Vargas e Silva Castanheira ◽  
...  
Keyword(s):  
Neutrophil Extracellular Traps ◽  
Organ Damage ◽  
Clinical Sepsis ◽  
Extracellular Traps

scholarly journals Neutrophil Extracellular Traps (NETs) in Severe SARS-CoV-2 Lung Disease

2021 ◽  
Vol 22 (16) ◽  
pp. 8854
Author(s):  
Monika Szturmowicz ◽  
Urszula Demkow
Keyword(s):  
Lung Injury ◽  
Nuclear Dna ◽  
Viral Infections ◽  
Prognostic Significance ◽  
Neutrophil Extracellular Traps ◽  
Organ Damage ◽  
Therapeutic Interventions ◽  
Extracellular Traps ◽  
Alveolar Capillary

Neutrophil extracellular traps (NETs), built from mitochondrial or nuclear DNA, proteinases, and histones, entrap and eliminate pathogens in the course of bacterial or viral infections. Neutrophils’ activation and the formation of NETs have been described as major risk factors for acute lung injury, multi-organ damage, and mortality in COVID-19 disease. NETs-related lung injury involves both epithelial and endothelial cells, as well as the alveolar-capillary barrier. The markers for NETs formation, such as circulating DNA, neutrophil elastase (NE) activity, or myeloperoxidase-DNA complexes, were found in lung specimens of COVID-19 victims, as well as in sera and tracheal aspirates obtained from COVID-19 patients. DNA threads form large conglomerates causing local obstruction of the small bronchi and together with NE are responsible for overproduction of mucin by epithelial cells. Various components of NETs are involved in the pathogenesis of cytokine storm in SARS-CoV-2 pulmonary disease. NETs are responsible for the interplay between inflammation and thrombosis in the affected lungs. The immunothrombosis, stimulated by NETs, has a poor prognostic significance. Better understanding of the role of NETs in the course of COVID-19 can help to develop novel approaches to the therapeutic interventions in this condition.

scholarly journals Targeting potential drivers of COVID-19: Neutrophil extracellular traps

2020 ◽  
Vol 217 (6) ◽  
Author(s):  
Betsy J. Barnes ◽  
Jose M. Adrover ◽  
Amelia Baxter-Stoltzfus ◽  
Alain Borczuk ◽  
Jonathan Cools-Lartigue ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Distress Syndrome ◽  
Cytokine Production ◽  
Neutrophil Extracellular Traps ◽  
Organ Damage ◽  
Clinical Severity ◽  
Pulmonary Diseases ◽  
Cytokine Storm ◽  
Extracellular Traps ◽  
Autopsy Specimen

Coronavirus disease 2019 (COVID-19) is a novel, viral-induced respiratory disease that in ∼10–15% of patients progresses to acute respiratory distress syndrome (ARDS) triggered by a cytokine storm. In this Perspective, autopsy results and literature are presented supporting the hypothesis that a little known yet powerful function of neutrophils—the ability to form neutrophil extracellular traps (NETs)—may contribute to organ damage and mortality in COVID-19. We show lung infiltration of neutrophils in an autopsy specimen from a patient who succumbed to COVID-19. We discuss prior reports linking aberrant NET formation to pulmonary diseases, thrombosis, mucous secretions in the airways, and cytokine production. If our hypothesis is correct, targeting NETs directly and/or indirectly with existing drugs may reduce the clinical severity of COVID-19.

Recombinant Thrombomodulin on Neutrophil Extracellular Traps in Murine Intestinal Ischemia–Reperfusion

2019 ◽  
Vol 131 (4) ◽  
pp. 866-882 ◽  
Author(s):  
Naoki Hayase ◽  
Kent Doi ◽  
Takahiro Hiruma ◽  
Ryo Matsuura ◽  
Yoshifumi Hamasaki ◽  
...  
Keyword(s):  
Intestinal Ischemia ◽  
Ischemia Reperfusion ◽  
Neutrophil Extracellular Traps ◽  
Organ Damage ◽  
Multiple Organ ◽  
Neutrophil Extracellular Trap ◽  
Blue Dye ◽  
Extracellular Traps ◽  
Recombinant Thrombomodulin ◽  
Intestinal Ischemia Reperfusion

Abstract Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background In multiple-organ dysfunction, an injury affecting one organ remotely impacts others, and the injured organs synergistically worsen outcomes. Recently, several mediators, including extracellular histones and neutrophil extracellular traps, were identified as contributors to distant organ damage. This study aimed to elucidate whether these mediators play a crucial role in remote organ damage induced by intestinal ischemia–reperfusion. This study also aimed to evaluate the protective effects of recombinant thrombomodulin, which has been reported to neutralize extracellular histones, on multiple-organ dysfunction after intestinal ischemia–reperfusion. Methods Intestinal ischemia was induced in male C57BL/6J mice via clamping of the superior mesenteric artery. Recombinant thrombomodulin (10 mg/kg) was administered intraperitoneally with the initiation of reperfusion. The mice were subjected to a survival analysis, histologic injury scoring, quantitative polymerase chain reaction analysis of tumor necrosis factor-α and keratinocyte-derived chemokine expression, Evans blue dye vascular permeability assay, and enzyme-linked immunosorbent assay analysis of histones in the jejunum, liver, lung, and kidney after 30- or 45-min ischemia. Neutrophil extracellular trap formation was evaluated by immunofluorescence staining. Results Recombinant thrombomodulin yielded statistically significant improvements in survival after 45-min ischemia (ischemia–reperfusion without vs. with 10 mg/kg recombinant thrombomodulin: 0% vs. 33%, n = 21 per group, P = 0.001). Recombinant thrombomodulin reduced the histologic injury score, expression of tumor necrosis factor-α and keratinocyte-derived chemokine, and extravasation of Evans blue dye, which were augmented by 30-min ischemia–reperfusion, in the liver, but not in the intestine. Accumulated histones and neutrophil extracellular traps were found in the livers and intestines of 30-min ischemia–reperfusion–injured mice. Recombinant thrombomodulin reduced these accumulations only in the liver. Conclusions Recombinant thrombomodulin improved the survival of male mice with intestinal ischemia–reperfusion injury. These findings suggest that histone and neutrophil extracellular trap accumulation exacerbate remote liver injury after intestinal ischemia–reperfusion. Recombinant thrombomodulin may suppress these accumulations and attenuate liver injury.

Circulating Extracellular DNA: Cause or Consequence of Thrombosis?

2017 ◽  
Vol 43 (06) ◽  
pp. 553-561 ◽  
Author(s):  
Miguel Jiménez-Alcázar ◽  
Natalie Kim ◽  
Tobias Fuchs
Keyword(s):  
Myocardial Infarction ◽  
Cell Injury ◽  
Thrombus Formation ◽  
Surrogate Marker ◽  
Neutrophil Extracellular Traps ◽  
Organ Damage ◽  
Extracellular Dna ◽  
Extracellular Traps

AbstractThrombosis leads to ischemic organ damage in cardiovascular and thromboembolic diseases. Neutrophils promote thrombosis in vitro and in vivo by releasing neutrophil extracellular traps (NETs). NETs are composed of DNA filaments coated with histones and neutrophil enzymes such as myeloperoxidase (MPO). Circulating extracellular DNA (ceDNA) is widely used as a surrogate marker to monitor NET formation in thrombosis. This narrative review summarizes the association of ceDNA with human thrombosis. Levels of ceDNA indicate the extent and outcome of several cardiovascular and thromboembolic diseases, including myocardial infarction, stroke, and venous thromboembolism. ceDNA correlates with markers of coagulation and platelet consumption, thus supporting the hypothesis that ceDNA may be a surrogate marker of thrombus formation. In addition, ceDNA levels correlate with markers of cell injury and size of ischemic lesions, suggesting that ceDNA does not derive from NETs but is probably released from damaged organs. Few studies identified NET-specific biomarkers such as DNA–MPO complexes in the blood of patients with thrombosis. In conclusion, it remains to be established whether ceDNA in patients derives from NETs and is a cause or consequence of thrombosis.

scholarly journals miR-146a in cardiovascular diseases and sepsis: an additional burden in the inflammatory balance?

2020 ◽  
Author(s):  
Ana Belen Arroyo ◽  
Sonia Águila ◽  
MARIA PIEDAD FERNANDEZ-PEREZ ◽  
ASCENSION M DE LOS REYES-GARCIA ◽  
Laura Reguilon-Gallego ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Neutrophil Extracellular Traps ◽  
Organ Damage ◽  
Regulatory Elements ◽  
Extracellular Traps ◽  
Whole Process ◽  
Additional Burden ◽  
Inflammatory Processes ◽  
Thrombotic Complications ◽  
Pathological Reaction

The new concept of thrombosis associated with an inflammatory process is called thromboinflammation. Indeed, both thrombosis and inflammation interplay one with the other in a feed forward manner amplifying the whole process. This pathological reaction in response to a wide variety of sterile or non-sterile stimuli eventually causes acute organ damage. In this context, neutrophils, mainly involved in eliminating pathogens as an early barrier to infection, form neutrophil extracellular traps (NETs) that are antimicrobial structures responsible of deleterious side effects such as thrombotic complications. Although NETosis mechanisms are being unraveled, there are still many regulatory elements that have to be discovered. miRNAs are important modulators of gene expression implicated in human pathophysiology almost two decades ago. Among the different miRNAs implicated in inflammation, miR-146a is of special interest because: (i) it regulates among others, TLR/NF-B axis which is of paramount importance in inflammatory processes, (ii) it regulates the formation of NETs by modifying their ageing phenotype, (iii) it has expression levels that may decrease among individuals up to 50%, controlled in part by the presence of several polymorphisms. In this manuscript, we will review the main characteristics of miR-146a biology. In addition, we will detail how miR-146a is implicated in the development of two paradigmatic diseases in which thrombosis and inflammation interact, cardiovascular diseases and sepsis, and their association with the presence of miR-146a polymorphisms and the use of miR-146a as a marker of cardiovascular diseases and sepsis.

scholarly journals Platelets and neutrophil extracellular traps collaborate to promote intravascular coagulation during sepsis in mice

Blood ◽  
2017 ◽  
Vol 129 (10) ◽  
pp. 1357-1367 ◽  
Author(s):  
Braedon McDonald ◽  
Rachelle P. Davis ◽  
Seok-Joo Kim ◽  
Mandy Tse ◽  
Charles T. Esmon ◽  
...  
Keyword(s):  
In Vivo Imaging ◽  
Neutrophil Extracellular Traps ◽  
Organ Damage ◽  
Microvascular Perfusion ◽  
Intravascular Coagulation ◽  
Extracellular Traps ◽  
Key Points

Key Points In vivo imaging reveals a NET–platelet–thrombin axis that promotes intravascular coagulation in sepsis. Inhibition of NETs during sepsis reduces intravascular coagulation, improves microvascular perfusion, and reduces organ damage.

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