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Extracellular Traps

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
Mary Clark, Jessica Kim, Neelou Etesami, Jacqueline Shimamoto, Ryan V Whalen, Gary Martin, Cheryl Y M Okumura
The resurgence of Group A Streptococcus (GAS) infections in the past two decades has been a rising major public health concern. Due to a large number of GAS infections occurring in the skin, mast cells (MCs), innate immune cells known to localize to the dermis, could play an important role in controlling infection. MCs can exert their antimicrobial activities either early during infection, by degranulation and release of antimicrobial proteases and the cathelicidin-derived antimicrobial peptide LL-37, or by forming antibacterial MC extracellular traps (MCETs) in later stages of infection...
2018: Frontiers in Immunology
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
Mao Li, Xi Chen, Jinku Yan, Long Zhou, Yifan Wang, Fan He, Jun Lin, Caihong Zhu, Guoqing Pan, Jia Yu, Ming Pei, Huilin Yang, Tao Liu
Decellularized extracellular matrix (ECM) derived from stem cells has been shown as a promising biomaterial for bone regeneration because of the promotion effect on osteogenesis in mesenchymal stem cells (MSCs). However, bone regeneration is also influenced by bone resorption and little is known about the effect of cell-derived ECM on osteoclast differentiation. In this study, ECM was deposited by MSCs and, after decellularization, the effect of ECM on osteoclastogenesis of bone marrow monocytes (BMMs) was investigated in comparison to standard tissue culture polystyrene...
March 8, 2018: Acta Biomaterialia
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
Mithun Ghosh, In Sook Kim, Young Min Lee, Seong Min Hong, Taek Hwan Lee, Ji Hong Lim, Trishna Debnath, Beong Ou Lim
This study aimed to determine the anti-osteoclastogenic effects of extracts from Aronia melanocarpa 'Viking' (AM) and identify the underlying mechanisms in vitro. Reactive oxygen species (ROS) are signal mediators in osteoclast differentiation. AM extracts inhibited ROS production in RAW 264.7 cells in a dose-dependent manner and exhibited strong radical scavenging activity. The extracts also attenuated the number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated osteoclasts. To attain molecular insights, the effect of the extracts on the signaling pathways induced by receptor activator of nuclear factor kappa B ligand (RANKL) were also investigated...
March 8, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
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
Xiaoli Tan, Shanqing Tao, Wenbo Liu, Antal Rockenbauer, Frederick A Villamena, Jay L Zweier, Yuguang Song, Yangping Liu
Electron paramagnetic resonance (EPR) spectroscopy coupled with the use of tetrathiatriarylmethyl (TAM) radicals has been a reliable method to detect superoxide radical (O2*-). However, the specificity and biocompatibility of TAM radicals need to be further improved. Although the derivatization may overcome the drawbacks of current TAM radicals, their esterification or amidation through the carboxylic groups greatly changes their redox properties and makes them inert to O2*-. Herein, we report the synthesis of a perthiatriarylmethyl (PST) radical and its dendritic derivatives PST-TA and PST-NA in which PST was covalently linked with the dendrons containing three and nine carboxylic acids (TA and NA), respectively...
March 5, 2018: Chemistry: a European Journal
Andrew Lichtman
Myoglobulin released from dead muscle is shown to induce acute kidney injury through a mechanism dependent on platelets and macrophage extracellular traps.
March 2, 2018: Science Immunology
L Martin, N Zouhiri, M Audran, A Marchand
New therapeutic proteins that trap circulating members of the TGF beta superfamily (activins and growth differentiation factors) show promising effects on erythropoiesis and muscular growth. They are dimeric recombinant fusion proteins composed of the extracellular domain of a human activin receptor (ActRIIA or IIB) linked to the Fc part of human IgG1. Sotatercept (ActRIIA-Fc) and Luspatercept (a modified ActRIIB-Fc) in particular are now in phase 2/3 of clinical trials against anemia and included in the prohibited list established by the World Anti-Doping Agency...
March 2, 2018: Drug Testing and Analysis
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