scholarly journals First observation of neutrophil extracellular traps in human leptospirosis

2017 ◽  
Vol 4 (4) ◽  
pp. 10 ◽  
Author(s):  
Emilia Scharrig ◽  
Ricardo Drut ◽  
Ricardo Martin Gomez
Keyword(s):  
Nuclear Dna ◽  
Febrile Illness ◽  
Neutrophil Extracellular Traps ◽  
Pulmonary Involvement ◽  
Human Leptospirosis ◽  
Extracellular Traps ◽  
Extracellular Release ◽  
Human Pathology ◽  
Life Threatening ◽  
First Time

Leptospirosis is the most important global zoonosis and is caused by pathogenic spirochetes of the genus Leptospira. Human leptospirosis ranges in severity from a mild, self-limited febrile illness to a fulminant life-threatening one but their pathogenesis is still unclear. The extracellular release of the nuclear DNA of neutrophils, called NETs, upon activation by microbes is a pathogen-killing mechanism of neutrophils described in 2004 although its presence in human pathology have been observed only very recently.We report a case of fatal fulminant leptospirosis with associated severe pulmonary involvement and shown for the first time, evidence of the presence of NETs in the lung tissue.

Formation of neutrophil extracellular traps requires actin cytoskeleton rearrangements

Blood ◽  
2022 ◽  
Author(s):  
Evelien G.G. Sprenkeler ◽  
Anton T.J. Tool ◽  
Stefanie Henriet ◽  
Robin van Bruggen ◽  
Taco W. Kuijpers
Keyword(s):  
Actin Polymerization ◽  
Nuclear Dna ◽  
Myosin Ii ◽  
Neutrophil Extracellular Traps ◽  
Actin Dynamics ◽  
Polymerization Process ◽  
Effector Cells ◽  
Extracellular Traps ◽  
Cytoskeleton Rearrangements ◽  
Cellular Components

Neutrophils are important effector cells in the host defense against invading micro-organisms. One of the mechanisms they employ to eliminate pathogens is the release of neutrophil extracellular traps (NETs). Although NET release and subsequent cell death known as NETosis have been intensively studied, the cellular components and factors determining or facilitating the formation of NETs remain incompletely understood. Using various actin polymerization and myosin II modulators on neutrophils from healthy individuals, we show that intact F-actin dynamics and myosin II function are essential for NET formation when induced by different stimuli, i.e. phorbol 12-myristate 13-acetate, monosodium urate crystals and Candida albicans. The role of actin polymerization in NET formation could not be explained by the lack of reactive oxygen species production or granule release, which were normal or enhanced under the given conditions. Neutrophils from patients with very rare inherited actin polymerization defects by either ARPC1B- or MKL1-deficiency also failed to show NETosis. We found that upon inhibition of actin dynamics there is a lack of translocation of NE to the nucleus, which may well explain the impaired NET formation. Collectively, our data illustrate the essential requirement of an intact and active actin polymerization process, as well as active myosin II to enable the release of nuclear DNA by neutrophils during NET formation.

scholarly journals How Neutrophil Extracellular Traps Become Visible

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Nicole de Buhr ◽  
Maren von Köckritz-Blickwede
Keyword(s):  
Electron Microscopy ◽  
Nuclear Dna ◽  
Defense Mechanism ◽  
Neutrophil Extracellular Traps ◽  
Immune Defense ◽  
Extracellular Traps ◽  
Activated Neutrophils ◽  
Microscopy Techniques

Neutrophil extracellular traps (NETs) have been identified as a fundamental innate immune defense mechanism against different pathogens. NETs are characterized as released nuclear DNA associated with histones and granule proteins, which form an extracellular web-like structure that is able to entrap and occasionally kill certain microbes. Furthermore, NETs have been shown to contribute to several noninfectious disease conditions when released by activated neutrophils during inflammation. The identification of NETs has mainly been succeeded by various microscopy techniques, for example, immunofluorescence microscopy, transmission electron microscopy (TEM), and scanning electron microscopy (SEM). Since the last years the development and improvement of new immunofluorescence-based techniques enabled optimized visualization and quantification of NETs. On the one handin vitrolive-cell imaging led to profound new ideas about the mechanisms involved in the formation and functionality of NETs. On the other hand different intravital,in vivo, andin situmicroscopy techniques led to deeper insights into the role of NET formation during health and disease. This paper presents an overview of the main used microscopy techniques to visualize NETs and describes their advantages as well as disadvantages.

scholarly journals Angiopoietin 1 release from human neutrophils is independent from neutrophil extracellular traps (NETs)

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Elcha Charles ◽  
Benjamin L. Dumont ◽  
Steven Bonneau ◽  
Paul-Eduard Neagoe ◽  
Louis Villeneuve ◽  
...  
Keyword(s):  
Nuclear Dna ◽  
Neutrophil Extracellular Traps ◽  
Innate Immune ◽  
Human Neutrophils ◽  
Extracellular Traps ◽  
Pathological Conditions ◽  
Healthy Control ◽  
Angiopoietin 1

Abstract Background Neutrophils induce the synthesis and release of angiopoietin 1 (Ang1), a cytosolic growth factor involved in angiogenesis and capable of inducing several pro-inflammatory activities in neutrophils. Neutrophils also synthesize and release neutrophil extracellular traps (NETs), comprised from decondensed nuclear DNA filaments carrying proteins such as neutrophil elastase (NE), myeloperoxidase (MPO), proteinase 3 (PR3) and calprotectin (S100A8/S100A9), which together, contribute to the innate immune response against pathogens (e.g., bacteria). NETs are involved in various pathological conditions through pro-inflammatory, pro-thrombotic and endothelial dysfunction effects and have recently been found in heart failure (HF) and type 2 diabetes (T2DM) patients. The aim of the present study was to investigate the role of NETs on the synthesis and release of Ang1 by the neutrophils in patients with T2DM and HF with preserved ejection fraction (HFpEF) (stable or acute decompensated; ADHFpEF) with or without T2DM. Results Our data show that at basal level (PBS) and upon treatment with LPS, levels of NETs are slightly increased in patients suffering from T2DM, HFpEF ± T2DM and ADHF without (w/o) T2DM, whereas this increase was significant in ADHFpEF + T2DM patients compared to healthy control (HC) volunteers and ADHFpEF w/o T2DM. We also observed that treatments with PMA or A23187 increase the synthesis of Ang1 (from 150 to 250%) in HC and this effect is amplified in T2DM and in all cohorts of HF patients. Ang1 is completely released (100%) by neutrophils of all groups and does not bind to NETs as opposed to calprotectin. Conclusions Our study suggests that severely ill patients with HFpEF and diabetes synthesize and release a greater abundance of NETs while Ang1 exocytosis is independent of NETs synthesis.

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 Netting Liver Disease: Neutrophil Extracellular Traps in the Initiation and Exacerbation of Liver Pathology

2020 ◽  
Vol 46 (06) ◽  
pp. 724-734 ◽  
Author(s):  
Fien A. von Meijenfeldt ◽  
Craig N. Jenne
Keyword(s):  
Liver Disease ◽  
Clinical Evidence ◽  
Nuclear Dna ◽  
Inflammatory Cells ◽  
Neutrophil Extracellular Traps ◽  
Blood Stream ◽  
Vital Role ◽  
Extracellular Traps ◽  
Thrombotic Complications ◽  
Pathogen Clearance

AbstractThe liver plays a vital role in the immune system. Its unique position in the portal circulation and the architecture of the hepatic sinusoids, in combination with the wide-ranged population of immunocompetent cells, make the liver function as an immune filter. To aid in pathogen clearance, once challenged, the liver initiates the rapid recruitment of a wide variety of inflammatory cells, including neutrophils. These neutrophils, in conjunction with platelets, facilitate the release of neutrophil extracellular traps (NETs), which are web-like structures of decondensed nuclear DNA, histones, and neutrophil proteins. NETs function as both a physical and a chemical barrier, binding and killing pathogens circulating in the blood stream. In addition to their antimicrobial role, NETs also bind platelets, activate coagulation, and exacerbate host inflammatory response. This interplay between inflammation and coagulation drives microvascular occlusion, ischemia, and (sterile) damage in liver disease. Although direct clinical evidence of this interplay is scarce, preliminary studies indicate that NETs contribute to progression of liver disease and (thrombotic) complications. Here, we provide an overview of the pathological mechanisms of NETs in liver disease. In addition, we summarize clinical evidence for NETs in different disease etiologies and complications of liver disease and discuss the possible implications for the use of NETs as a diagnostic marker and a therapeutic target in liver disease.

scholarly journals SP-D attenuates LPS-induced formation of human neutrophil extracellular traps (NETs), protecting pulmonary surfactant inactivation by NETs

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Raquel Arroyo ◽  
Meraj Alam Khan ◽  
Mercedes Echaide ◽  
Jesús Pérez-Gil ◽  
Nades Palaniyar
Keyword(s):  
Pulmonary Surfactant ◽  
Lung Surfactant ◽  
Neutrophil Extracellular Traps ◽  
Surfactant Protein ◽  
Human Neutrophils ◽  
Surfactant Protein D ◽  
Host Proteins ◽  
Extracellular Traps ◽  
Surface Active Properties ◽  
First Time

AbstractAn exacerbated amount of neutrophil extracellular traps (NETs) can cause dysfunction of systems during inflammation. However, host proteins and factors that suppress NET formation (NETosis) are not clearly identified. Here we show that an innate immune collectin, pulmonary surfactant protein-D (SP-D), attenuates lipopolysaccharide (LPS)-mediated NETosis in human neutrophils by binding to LPS. SP-D deficiency in mice (Sftpd−/−) leads to excess NET formation in the lungs during LPS-mediated inflammation. In the absence of SP-D, NETs inhibit the surface-active properties of lung surfactant, essential to prevent the collapse of alveoli, the air breathing structures of the lungs. SP-D reverses NET-mediated inhibition of surfactant and restores the biophysical properties of surfactant. To the best of our knowledge, this study establishes for the first time that (i) SP-D suppresses LPS-mediated NETosis, (ii) NETs inhibit pulmonary surfactant function in the absence of SP-D, and (iii) SP-D can restore NET-mediated inhibition of the surfactant system.

scholarly journals Angiopoietin 1 release from Human Neutrophils is Independent from Neutrophil Extracellular Traps (NETs)

2021 ◽  
Author(s):  
Elcha Charles ◽  
Benjamin Dumont ◽  
Steven Bonneau ◽  
Paul-Eduard Neagoe ◽  
Louis Villeneuve ◽  
...  
Keyword(s):  
Nuclear Dna ◽  
Neutrophil Extracellular Traps ◽  
Innate Immune ◽  
Human Neutrophils ◽  
Extracellular Traps ◽  
Pathological Conditions ◽  
Healthy Control ◽  
Angiopoietin 1

Abstract Background: Neutrophils induce the synthesis and release of angiopoietin 1 (Ang1), a cytosolic growth factor involved in angiogenesis and capable of inducing several pro-inflammatory activities in neutrophils. Neutrophils also synthesize and release neutrophil extracellular traps (NETs), comprised from decondensed nuclear DNA filaments carrying proteins such as neutrophil elastase (NE), myeloperoxidase (MPO), proteinase 3 (PR3) and calprotectin (S100A8/S100A9), which together, contribute to the innate immune response against pathogens (e.g., bacteria). NETs are involved in various pathological conditions through pro-inflammatory, pro-thrombotic and endothelial dysfunction effects and have recently been found in heart failure (HF) and type 2 diabetes (T2DM) patients. The aim of the present study was to investigate the role of NETs on the synthesis and release of Ang1 by the neutrophils in patients with T2DM and HF with preserved ejection fraction (HFpEF) (stable or acute decompensated; ADHFpEF) with or without T2DM. Results: Our data show that at basal level (PBS) and upon treatment with LPS, levels of NETs are slightly increased in patients suffering from T2DM, HFpEF ± T2DM and ADHF w/o T2DM, whereas this increase was significant in ADHFpEF + T2DM patients compared to healthy control (HC) volunteers and ADHFpEF without T2DM. We also observed that treatments with PMA or A23187 increase the synthesis of Ang1 (from 150 to 250%) in HC and this effect is amplified in T2DM and in all cohorts of HF patients. Ang1 is completely released (100%) by neutrophils of all groups and does not bind to NETs as opposed to calprotectin. Conclusions: Our study suggests that severely ill patients with HFpEF and diabetes synthesize and release a greater abundance of NETs while Ang1 exocytosis is independent of NETs synthesis.

scholarly journals Neutrophil Extracellular Traps (NETs): Opportunities for Targeted Therapy

Acta Naturae ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 15-23
Author(s):  
Dmitry V. Volkov ◽  
George V. Tetz ◽  
Yury P. Rubtsov ◽  
Alexey V. Stepanov ◽  
Alexander G. Gabibov
Keyword(s):  
Solid Tumors ◽  
Nuclear Dna ◽  
Neutrophil Extracellular Traps ◽  
Dnase I ◽  
Extracellular Traps ◽  
Leading Role ◽  
Deoxyribonuclease I ◽  
Car T ◽  
Main Component

Antitumor therapy, including adoptive immunotherapy, inevitably faces powerful counteraction from advanced cancer. If hematological malignancies are currently amenable to therapy with CAR-T lymphocytes (T-cells modified by the chimeric antigen receptor), solid tumors, unfortunately, show a significantly higher degree of resistance to this type of therapy. As recent studies show, the leading role in the escape of solid tumors from the cytotoxic activity of immune cells belongs to the tumor microenvironment (TME). TME consists of several types of cells, including neutrophils, the most numerous cells of the immune system. Recent studies show that the development of the tumor and its ability to metastasize directly affect the extracellular traps of neutrophils (neutrophil extracellular traps, NETs) formed as a result of the response to tumor stimuli. In addition, the nuclear DNA of neutrophils the main component of NETs erects a spatial barrier to the interaction of CAR-T with tumor cells. Previous studies have demonstrated the promising potential of deoxyribonuclease I (DNase I) in the destruction of NETs. In this regard, the use of eukaryotic deoxyribonuclease I (DNase I) is promising in the effort to increase the efficiency of CAR-T by reducing the NETs influence in TME. We will examine the role of NETs in TME and the various approaches in the effort to reduce the effect of NETs on a tumor.

Neutrophil extracellular traps contain mitochondrial as well as nuclear DNA and exhibit inflammatory potential

2011 ◽  
Vol 81A (3) ◽  
pp. 238-247 ◽  
Author(s):  
Ravi S. Keshari ◽  
Anupam Jyoti ◽  
Sachin Kumar ◽  
Megha Dubey ◽  
Anupam Verma ◽  
...  
Keyword(s):  
Nuclear Dna ◽  
Neutrophil Extracellular Traps ◽  
Extracellular Traps

scholarly journals Neutrophil extracellular traps mediate transfer of cytoplasmic neutrophil antigens to myeloid dendritic cells toward ANCA induction and associated autoimmunity

Blood ◽  
2012 ◽  
Vol 120 (15) ◽  
pp. 3007-3018 ◽  
Author(s):  
Sabina Sangaletti ◽  
Claudio Tripodo ◽  
Claudia Chiodoni ◽  
Carla Guarnotta ◽  
Barbara Cappetti ◽  
...  
Keyword(s):  
Cell Death ◽  
Dendritic Cells ◽  
Structural Integrity ◽  
Neutrophil Extracellular Traps ◽  
Antineutrophil Cytoplasmic Antibodies ◽  
Small Vessel Vasculitis ◽  
Myeloid Dendritic Cells ◽  
Extracellular Traps ◽  
Cytoplasmic Proteins ◽  
Human Pathology

Abstract Antineutrophil cytoplasmic antibodies (ANCAs) target proteins normally retained within neutrophils, indicating that cell death is involved in the autoimmunity process. Still, ANCA pathogenesis remains obscure. ANCAs activate neutrophils inducing their respiratory burst and a peculiar form of cell death, named NETosis, characterized by formation of neutrophil extracellular traps (NETs), decondensed chromatin threads decorated with cytoplasmic proteins endorsed with antimicrobial activity. NETs have been consistently detected in ANCA-associated small-vessel vasculitis, and this association prompted us to test whether the peculiar structure of NET favors neutrophil proteins uploading into myeloid dendritic cells and the induction of ANCAs and associated autoimmunity. Here we show that myeloid DCs uploaded with and activated by NET components induce ANCA and autoimmunity when injected into naive mice. DC uploading and autoimmunity induction are prevented by NET treatment with DNAse, indicating that NET structural integrity is needed to maintain the antigenicity of cytoplasmic proteins. We found NET intermingling with myeloid dendritic cells also positive for neutrophil myeloperoxidase in myeloperoxidase-ANCA-associated microscopic poliangiitis providing a potential correlative picture in human pathology. These data provide the first demonstration that NET structures are highly immunogenic such to trigger adaptive immune response relevant for autoimmunity.

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