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Neutrophil extracellular trap

Lisa Menegazzo, Valentina Scattolini, Roberta Cappellari, Benedetta Maria Bonora, Mattia Albiero, Mario Bortolozzi, Filippo Romanato, Giulio Ceolotto, Saula Vigili de Kreutzeberg, Angelo Avogaro, Gian Paolo Fadini
AIMS: Diabetes is associated with an excess release of neutrophil extracellular traps (NETs) and an enhanced NETosis, a neutrophil cell death programme instrumental to anti-microbial defences, but also involved in tissue damage. We herein investigated whether the antidiabetic drug metformin protects against NETosis. METHODS: We measured NET components in the plasma of patients with pre-diabetes who were randomized to receive metformin or placebo for 2 months. To control for the effect on glucose, we also measured NET components in the plasma of patients with type 2 diabetes before and after treatment with insulin or dapagliflozin...
March 15, 2018: Acta Diabetologica
Stella Arelaki, Athanasios Arampatzioglou, Konstantinos Kambas, Efthimios Sivridis, Alexandra Giatromanolaki, Konstantinos Ritis
Inflammation is a hallmark of colorectal cancer (CRC). Neutrophils are well-known mediators in tumor biology but their role in solid tumors, including CRC, was redefined by neutrophil extracellular traps (NETs). Given that it was recently demonstrated that platelet-derived polyP primes neutrophils to release NETs, we examined surgical specimens from CRC to investigate the presence of polyP, as a possible NET inducer. Biopsies with adenomas, hyperplastic polyps, inflammatory bowel disease and healthy colon tissues were used as controls...
2018: PloS One
Kristof Van Avondt, Dominik Hartl
While the microscopic appearance of neutrophil extracellular traps (NETs) has fascinated basic researchers since its discovery, the (patho)physiological mechanisms triggering NET release, the disease relevance and clinical translatability of this unconventional cellular mechanism remained poorly understood. Here we summarize and discuss current concepts of the mechanisms and disease relevance of NET formation. This article is protected by copyright. All rights reserved.
March 15, 2018: European Journal of Clinical Investigation
Gabriel Sollberger, Dorothea Ogmore Tilley, Arturo Zychlinsky
Neutrophils are essential to the homeostatic mission of safeguarding host tissues, responding rapidly and diversely to breaches of the host's barriers to infection, and returning tissues to a sterile state. In response to specific stimuli, neutrophils extrude modified chromatin structures decorated with specific cytoplasmic and granular proteins called neutrophil extracellular traps (NETs). Several pathways lead to this unique form of cell death (NETosis). Extracellular chromatin may have evolved to defend eukaryotic organisms against infection, and its release has at least three functions: trapping and killing of microbes, amplifying immune responses, and inducing coagulation...
March 12, 2018: Developmental Cell
Lu Li, Hai-Dong Fu
Neutrophil extracellular traps (NETs) represent a form of cell death distinct from apoptosis or necrosis. The imbalance between the formation and degradation of NETs has long been considered to be closely associated with the activity of autoimmune diseases such as systemic lupus erythematous (SLE). Reactive oxygen species derived from the nicotinamide adenine dinucleotide phosphate oxidase pathway or mitochondrial DNA pathway play a key role in the primary stage of NETs formation. The exposure or delayed degradation of abundant autoantigens, such as double-strand DNA, caused by abnormal activation of neutrophils can induce autoantibody to form immune complexes that deposit in local tissues and then induce the plasmacytoid dendritic cells to secrete the interferon alpha and other inflammatory factors...
March 2018: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
Silvia D Visonà, Onno J de Boer, Claire Mackaaij, Hans H de Boer, Kartika R Pertiwi, Ruben W de Winter, Antonio Osculati, Allard C van der Wal
Acute medial dissection of aorta can occur in the context of a sudden and unexpected death. For medico-legal reasons it is important to estimate as accurately the histological age of dissections. We evaluated the additional value of a systematic application of immunohistochemistry, compared with conventional histology only, in determining chronological steps of injury and repair. Thirty two paraffin embedded specimens of aortic dissection were retrospectively allocated to one of four defined stages: acute (I), subacute (II), early organizing (III) and scarring (IV) using Hematoxylin and Eosin and Elastica van Gieson stained sections...
February 10, 2018: Cardiovascular Pathology: the Official Journal of the Society for Cardiovascular Pathology
K H Lee, L Cavanaugh, H Leung, F Yan, Z Ahmadi, B H Chong, F Passam
INTRODUCTION: Neutrophil extracellular traps (NETs) are networks of extracellular fibres produced from neutrophil DNA with a pathogenic role in infection, thrombosis and other conditions. Reliable assays for measuring NETs are desirable as novel treatments targeting NETs are being explored for the treatment of these conditions. We compare a whole blood flow cytometry method with serum assays to measure NETs-associated markers in patients with sepsis and thrombosis. METHODS: Patients with deep venous thrombosis (n = 25), sepsis (n = 21) and healthy controls (n = 23) were included in the study...
March 9, 2018: International Journal of Laboratory Hematology
Fahim Ebrahimi, Stavros Giaglis, Sinuhe Hahn, Claudine A Blum, Christine Baumgartner, Alexander Kutz, Shane Vontelin van Breda, Beat Mueller, Philipp Schuetz, Mirjam Christ-Crain, Paul Hasler
Neutrophil extracellular traps (NETs) are a hallmark of the immune response in inflammatory diseases. However, the role of NETs in community-acquired pneumonia is unknown. This study aims to characterise the impact of NETs on clinical outcomes in pneumonia.This is a secondary analysis of a randomized-controlled, multicentre trial. Patients with community-acquired pneumonia were randomly assigned to either prednisone 50 mg or placebo for 7 days. The primary endpoint was time to clinical stability; main secondary endpoints were length of hospital stay and mortality...
March 8, 2018: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
Raphaël Coscas, Sebastien Dupont, Sacha Mussot, Liliane Louedec, Harry Etienne, Marion Morvan, Gilles Chiocchia, Ziad Massy, Marie-Paule Jacob, Jean-Baptiste Michel
BACKGROUND: Recent evidence suggests that adaptive immunity develops during abdominal aortic aneurysm evolution. Uncertainties remain about the antigens implicated and their role in inducing rupture. Because antigens from the extracellular matrix (ECM) have been suspected, the aim of this experimental study was to characterize the role of adaptive immunity directed against antigens from the aortic ECM. METHODS: In a first step, an experimental model of abdominal aortic aneurysm rupture based on adaptive immunity against the ECM was developed and characterized...
March 5, 2018: Journal of Vascular Surgery
Jon M Florence, Agnieszka Krupa, Laela M Booshehri, Sandra A Davis, Michael A Matthay, Anna K Kurdowska
Infection with seasonal influenza A virus (IAV) leads to lung inflammation and respiratory failure, a main cause of death in influenza infected patients. Previous experiments in our laboratory indicated that Bruton's tyrosine kinase (Btk) plays a substantial role in regulating inflammation in the respiratory region during acute lung injury (ALI) in mice, therefore we sought to determine if blocking Btk activity had a protective effect in the lung during influenza induced inflammation. A Btk inhibitor (Btk Inh...
March 8, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
Angelo A Manfredi, Giuseppe A Ramirez, Patrizia Rovere-Querini, Norma Maugeri
Neutrophils recognize particulate substrates of microbial or endogenous origin and react by sequestering the cargo via phagocytosis or by releasing neutrophil extracellular traps (NETs) outside the cell, thus modifying and alerting the environment and bystander leukocytes. The signals that determine the choice between phagocytosis and the generation of NETs are still poorly characterized. Neutrophils that had phagocytosed bulky particulate substrates, such as apoptotic cells and activated platelets, appear to be "poised" in an unresponsive state...
2018: Frontiers in Immunology
Carlos Rosales
Neutrophils are the most abundant leukocytes in the circulation, and have been regarded as first line of defense in the innate arm of the immune system. They capture and destroy invading microorganisms, through phagocytosis and intracellular degradation, release of granules, and formation of neutrophil extracellular traps after detecting pathogens. Neutrophils also participate as mediators of inflammation. The classical view for these leukocytes is that neutrophils constitute a homogenous population of terminally differentiated cells with a unique function...
2018: Frontiers in Physiology
Naveen Gupta, Roland Liu, Stephanie Shin, Ranjeet Sinha, Joseph Pogliano, Kit Pogliano, John H Griffin, Victor Nizet, Ross Corriden
Objectives: The role of protease-activated receptor 1 (PAR1) in the pathogenesis of pneumonia and sepsis is ambiguous given the existing literature. As PAR1 is classically activated by the coagulation-based protease thrombin and leads to vascular leakage, our hypothesis was that PAR1 blockade with SCH79797 would be therapeutically beneficial in an experimental model of murine Gram-negative pneumonia. Methods: In this study, we administered SCH79797 via the intrapulmonary route 6 h after the establishment of Escherichia coli pneumonia and observed a significant improvement in survival, lung injury, bacterial clearance and inflammation...
March 5, 2018: Journal of Antimicrobial Chemotherapy
Yongzhi Wang, Lingtao Luo, Oscar Ö Braun, Johannes Westman, Raed Madhi, Heiko Herwald, Matthias Mörgelin, Henrik Thorlacius
Abdominal sepsis is associated with dysfunctional hemostasis. Thrombin generation (TG) is a rate-limiting step in systemic coagulation. Neutrophils can expell neutrophil extracellular traps (NETs) and/or microparticles (MPs) although their role in pathological coagulation remains elusive. Cecal ligation and puncture (CLP)-induced TG in vivo was reflected by a reduced capacity of plasma from septic animals to generate thrombin. Depletion of neutrophils increased TG in plasma from CLP mice. Sepsis was associated with increased histone 3 citrullination in neutrophils and plasma levels of cell-free DNA and DNA-histone complexes and administration of DNAse not only eliminated NET formation but also elevated TG in sepsis...
March 5, 2018: Scientific Reports
Meraj A Khan, Lijy M Philip, Guillaume Cheung, Shawn Vadakepeedika, Hartmut Grasemann, Neil Sweezey, Nades Palaniyar
Neutrophils migrating from the blood (pH 7.35-7.45) into the surrounding tissues encounter changes in extracellular pH (pHe ) conditions. Upon activation of NADPH oxidase 2 (Nox), neutrophils generate large amounts of H+ ions reducing the intracellular pH (pHi ). Nevertheless, how extracellular pH regulates neutrophil extracellular trap (NET) formation (NETosis) is not clearly established. We hypothesized that increasing pH increases Nox-mediated production of reactive oxygen species (ROS) and neutrophil protease activity, stimulating NETosis...
2018: Frontiers in Medicine
Peiwu Ding, Shaoshao Zhang, Miao Yu, Yuqian Feng, Qi Long, Huimin Yang, Jingdong Li, Min Wang
Deep venous thrombosis (DVT) is a significant problem in the health care industry worldwide. However, the factors and signaling pathways that trigger DVT formation are still largely unknown. In this study, we investigated the role of interleukin-17A (IL-17A) in DVT formation, focusing on the role of platelet aggregation, neutrophil infiltration, and endothelium cell (EC) activation. Notably, IL-17A levels increased in DVT patients as well as in a mouse DVT model. The DVT model mice were injected with recombinant mouse-IL-17A (rIL-17A) or anti-IL-17A monoclonal antibody (mAb) to further evaluate the effects of this cytokine...
February 23, 2018: International Immunopharmacology
Barbora Konečná, Lucia Lauková, Barbora Vlková
Cell-free self-DNA or RNA may induce an immune response by activating specific sensing receptors. During pregnancy, placental nucleic acids present in the maternal circulation further activate these receptors due to the presence of unmethylated CpG islands. A higher concentration of cell-free fetal DNA is associated with pregnancy complications and a higher risk for fetal rejection. Cell-free fetal DNA originates from placental trophoblasts. It appears in different forms: free, bound to histones in nucleosomes, in neutrophil extracellular traps and in extracellular vesicles...
February 26, 2018: Scandinavian Journal of Immunology
Miguel Jiménez-Alcázar, Andreas Limacher, Rachita Panda, Marie Méan, Josephine Bitterling, Sven Peine, Thomas Renné, Jürg H Beer, Drahomir Aujesky, Bernhard Lämmle, Tobias A Fuchs
BACKGROUND: Venous thromboembolism (VTE) is a major cause of morbidity and mortality in elderly patients. Extracellular DNA is a pro-inflammatory and pro-thrombotic mediator in vitro and in animal models. Levels of circulating extracellular DNA (ceDNA) are increased in VTE patients, but the association of ceDNA with VTE extent and clinical outcome is poorly understood. OBJECTIVES: We analyzed the association of ceDNA with the extent of VTE, categorized as distal and proximal deep vein thrombosis and pulmonary embolism, and with the clinical outcomes VTE recurrence and mortality...
2018: PloS One
Miriam Sjåstad Langseth, Trine Baur Opstad, Vibeke Bratseth, Svein Solheim, Harald Arnesen, Alf Åge Pettersen, Ingebjørg Seljeflot, Ragnhild Helseth
Background Neutrophil extracellular traps, comprising chromatin and granule proteins, have been implicated in atherothrombosis. Design and methods We investigated whether the circulating neutrophil extracellular traps markers, double-stranded DNA and myeloperoxidase-DNA were associated with clinical outcome and hypercoagulability in patients with stable coronary artery disease. Patients with angiographically verified stable coronary artery disease ( n = 1001) were included. Follow-up was 2 years, recording 106 clinical endpoints (unstable angina, non-haemorrhagic stroke, myocardial infarction or death)...
January 1, 2018: European Journal of Preventive Cardiology
Akshaya K Meher, Michael Spinosa, John P Davis, Nicolas Pope, Victor E Laubach, Gang Su, Vlad Serbulea, Norbert Leitinger, Gorav Ailawadi, Gilbert R Upchurch
OBJECTIVE: Neutrophils promote experimental abdominal aortic aneurysm (AAA) formation via a mechanism that is independent from MMPs (matrix metalloproteinases). Recently, we reported a dominant role of IL (interleukin)-1β in the formation of murine experimental AAAs. Here, the hypothesis that IL-1β-induced neutrophil extracellular trap formation (NETosis) promotes AAA was tested. APPROACH AND RESULTS: NETs were identified through colocalized staining of neutrophil, Cit-H3 (citrullinated histone H3), and DNA, using immunohistochemistry...
February 22, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
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