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Neutrophil extracellular traps

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https://www.readbyqxmd.com/read/29133856/therapeutic-targeting-of-extracellular-dna-improves-the-outcome-of-intestinal-ischemic-reperfusion-injury-in-neonatal-rats
#1
Michael Boettcher, Georg Eschenburg, Stefan Mietzsch, Miguel Jiménez-Alcázar, Michaela Klinke, Deirdre Vincent, Bastian Tiemann, Robert Bergholz, Konrad Reinshagen, Tobias A Fuchs
Thrombosis and inflammation cooperate in the development of intestinal infarction. Recent studies suggest that extracellular DNA released by damaged cells or neutrophils in form of extracellular traps (NETs) contributes to organ damage in experimental models of ischemia-reperfusion injury. Here we compared the therapeutic effects of targeting fibrin or extracellular DNA in intestinal infarction after midgut volvulus in rats. Following iatrogenic midgut volvulus induction for 3 hours, we treated animals with a combination of tissue plasminogen activator (tPA) and low molecular weight heparin (LMWH) to target fibrin or with DNase1 to degrade extracellular DNA...
November 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29129225/lipopolysaccharide-induced-neutrophil-extracellular-trap-formation-in-canine-neutrophils-is-dependent-on-histone-h3-citrullination-by-peptidylarginine-deiminase
#2
Ronald H L Li, Geena Ng, Fern Tablin
Neutrophils release neutrophil extracellular traps (NETs), which are extracellular chromatin decorated with histones and antimicrobial proteins. Although known for antimicrobial properties, overzealous production of NETs (NETosis) may lead to cytotoxicity and multiple organ failure in sepsis. Pathogen-induced NETosis has been extensively studied in mice but its importance in dogs remains largely unknown. This study sought to characterize in vitro NETosis induced by E.coli LPS, including assessing the role of peptidylarginine deiminase (PAD) in canine NETosis...
December 2017: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/29124783/a-key-role-for-rac-and-pak-signaling-in-neutrophil-extracellular-traps-nets-formation-defines-a-new-potential-therapeutic-target
#3
M Gavillet, K Martinod, R Renella, D D Wagner, D A Williams
NET formation in mice (NETosis) is supported by reactive oxygen species (ROS) production by NADPH oxidase and histone hypercitrullination by peptidylarginine deiminase 4 (PAD4). Rac1 and Rac2, expressed in polymorphonuclear neutrophils (PMNs), regulate the cytoskeleton, cell shape, adhesion and migration and are also essential components of the NADPH oxidase complex. We aimed to explore the role of the Rac signaling pathway including the upstream guanosine exchange factor (GEF) activator, Vav, and a downstream effector, the p21-activated kinase, Pak, on NETosis in PMNs using a previously described flow-cytometry-based assay...
November 10, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/29123528/janus-faced-neutrophil-extracellular-traps-in-periodontitis
#4
REVIEW
Ljubomir Vitkov, Dominik Hartl, Bernd Minnich, Matthias Hannig
Periodontitis is characterized by PMN infiltration and formation of neutrophil extracellular traps (NETs). However, their functional role for periodontal health remains complex and partially understood. The main function of NETs appears to be evacuation of dental plaque pathogen-associated molecular patterns. The inability to produce NETs is concomitant with aggressive periodontitis. But in cases with exaggerated NET production, NETs are unable to maintain periodontal health and bystander damages occur. This pathology can be also demonstrated in animal models using lipopolysaccharide as PMN activator...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29121457/drugs-implicated-in-systemic-autoimmunity-modulate-neutrophil-extracellular-trap-formation
#5
Jorge A Irizarry-Caro, Carmelo Carmona-Rivera, Daniella M Schwartz, Sami S Khaznadar, Mariana J Kaplan, Peter C Grayson
OBJECTIVE: Aberrant neutrophil extracellular trap (NET) formation has been implicated as a mechanism to induce auto-reactivity in at-risk individuals. The study objective was to assess whether medications implicated in cases of drug-induced autoimmunity (hydralazine and procainamide) and medications less commonly associated with drug-induced autoimmunity (minocycline and clozapine) induce NET formation and/or prevent NET degradation. METHODS: Human neutrophils were incubated with the drugs of interest and resultant NET formation was quantified by fluorescent microscopy...
November 9, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29117594/histones-and-chymotrypsin-like-elastases-play-significant-roles-in-the-antimicrobial-activity-of-tongue-sole-neutrophil-extracellular-traps
#6
Li-Lian Wen, Ming-Li Zhao, Heng Chi, Li Sun
Neutrophil extracellular traps (NETs) are a form of extracellular antimicrobial structure of neutrophils observed in higher and lower vertebrates, the latter including the teleost fish tongue sole Cynoglossus semilaevis. However, the antimicrobial mechanism of fish NETs is unknown. In the present study, we examined the potential contribution of histones and elastases to the antibacterial effect of tongue sole NETs. For this purpose, two histones (CsH2B and CsH4) and two elastases (CsEla1 and CsEla2) of tongue sole were investigated...
November 5, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29107075/the-role-of-extracellular-histones-in-influenza-virus-pathogenesis
#7
Harshini K Ashar, Nathan C Mueller, Jennifer M Rudd, Timothy A Snider, Mallika Achanta, Maram Prasanthi, Sivasami Pulavendran, Paul G Thomas, Ramachandran Akhilesh, Jerry R Malayer, Jerry W Ritchey, Rachakatla Rajasekhar, Vincent Tk Chow, Charles T Esmon, Narasaraju Teluguakula
Although exaggerated host immune responses have been implicated in influenza-induced lung pathogenesis, the etiologic factors that contribute to these events are not completely understood. We previously demonstrated that neutrophil extracellular traps exacerbate pulmonary injury during influenza pneumonia. Histones are the major protein components of neutrophil extracellular traps and are known to have cytotoxic effects. Here, we examined the role of extracellular histones in lung pathogenesis during influenza...
October 26, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/29106059/increased-levels-of-neutrophil-extracellular-trap-remnants-in-the-serum-of-patients-with-rheumatoid-arthritis
#8
Wei Wang, Wanchan Peng, Xingwang Ning
AIMS: Neutrophil extracellular traps (NETs) comprise a unique form of non-apoptotic cell death exhibited by neutrophils, which occurs in a stepwise process termed NETosis. It has been postulated that NETosis plays an important role in the pathogenesis of autoimmune disorders. The aim of this study was to evaluate serum levels of NET remnants in patients with rheumatoid arthritis (RA), as well as potential associations between NET remnants and indicators of RA. METHODS: Serum levels of myeloperoxidase (MPO)-DNA complexes (NET remnants) were examined in 74 RA patients and 50 healthy controls using a modified enzyme-linked immunosorbent assay...
November 6, 2017: International Journal of Rheumatic Diseases
https://www.readbyqxmd.com/read/29103955/cell-cycle-proteins-control-production-of-neutrophil-extracellular-traps
#9
Borko Amulic, Sebastian Lorenz Knackstedt, Ulrike Abu Abed, Nikolaus Deigendesch, Christopher J Harbort, Brian E Caffrey, Volker Brinkmann, Frank L Heppner, Philip W Hinds, Arturo Zychlinsky
Neutrophils are essential for immune defense and can respond to infection by releasing chromatin in the form of neutrophil extracellular traps (NETs). Here we show that NETs are induced by mitogens and accompanied by induction of cell-cycle markers, including phosphorylation of the retinoblastoma protein and lamins, nuclear envelope breakdown, and duplication of centrosomes. We identify cyclin-dependent kinases 4 and 6 (CDK4/6) as essential regulators of NETs and show that the response is inhibited by the cell-cycle inhibitor p21(Cip)...
October 31, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29102925/role-for-neutrophil-extracellular-traps-nets-and-platelet-aggregation-in-early-sepsis-induced-hepatic-dysfunction
#10
Kentaro Sakurai, Tomoharu Miyashita, Mitsuyoshi Okazaki, Takahisa Yamaguchi, Yoshinao Ohbatake, Shinichi Nakanuma, Koichi Okamoto, Seisho Sakai, Jun Kinoshita, Isamu Makino, Keishi Nakamura, Hironori Hayashi, Katsunobu Oyama, Hidehiro Tajima, Hiroyuki Takamura, Itasu Ninomiya, Sachio Fushida, Kenichi Harada, John W Harmon, Tetsuo Ohta
BACKGROUND/AIM: Severe sepsis is associated with high morbidity and mortality rates. Inflammation and coagulation play pivotal roles in the pathogenesis of sepsis leading to multiple organ failure, especially in the liver. The aim of the present study was to assess the mechanism from sepsis to liver damage in a mouse model. MATERIALS AND METHODS: We created a sepsis model by injecting lipopolysaccharide (LPS) intraperitoneally in mice. At 0, 6, 12, and 24 h following intraperitoneal injection of LPS, mice were euthanised and analyzed...
November 2017: In Vivo
https://www.readbyqxmd.com/read/29101355/particles-of-different-sizes-and-shapes-induce-neutrophil-necroptosis-followed-by-the-release-of-neutrophil-extracellular-trap-like-chromatin
#11
Jyaysi Desai, Orestes Foresto-Neto, Mohsen Honarpisheh, Stefanie Steiger, Daigo Nakazawa, Bastian Popper, Eva Miriam Buhl, Peter Boor, Shrikant R Mulay, Hans-Joachim Anders
The human body is exposed to a wide range of particles of industrial, environmental or internal origin such as asbestos, alum, silica or crystals of urate, calcium phosphate, calcium oxalate, cystine or cholesterol. Phagocytic clearance of such particles involves neutrophils and macrophages. Here we report that neutrophils encountering such particles of diverse sizes and shapes undergo necrotic cell death, a process associated with the formation of neutrophil extracellular trap (NET)-like extracellular DNA...
November 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29100671/-nettling-the-host-breaking-of-tolerance-in-chronic-inflammation-and-chronic-infection
#12
REVIEW
Sladjana Skopelja-Gardner, Jonathan D Jones, William F C Rigby
How and why we break tolerance to self-proteins still remains a largely unanswered question. Neutrophils have been identified as a rich source of autoantigens in a wide array of autoimmune diseases that arise as a consequence of different environmental and genetic factors, e.g. rheumatoid arthritis (RA), lupus, vasculitis, cystic fibrosis (CF) etc. Specifically, neutrophil extracellular trap (NET) formation has been identified as a link between innate and adaptive immune responses in autoimmunity. Autoantigens including neutrophil granular proteins (targeted by anti-neutrophil cytoplasmic antibodies, ANCA) as well as post-translationally modified proteins, i...
October 31, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29093651/current-understanding-in-neutrophil-differentiation-and-heterogeneity
#13
REVIEW
Chang-Won Hong
Neutrophils are professional phagocytes that conduct effectors functions in the innate immune systems. They are differentiated in the bone marrow (BM) and terminally differentiated neutrophils are then released into systemic circulation. Neutrophils migrate into inflammatory foci through extravasation, reverse transmigration, and chemotaxis. As neutrophils arrive at a target site, they actively participate in eliminating pathogens. They phagocytose bacteria, and eliminate them through the generation of reactive oxygen species (ROS), release of protease-enriched granules, and formation of neutrophil extracellular traps (NETs)...
October 2017: Immune Network
https://www.readbyqxmd.com/read/29078325/necroptosis-controls-net-generation-and-mediates-complement-activation-endothelial-damage-and-autoimmune-vasculitis
#14
Adrian Schreiber, Anthony Rousselle, Jan Ulrich Becker, Anne von Mässenhausen, Andreas Linkermann, Ralph Kettritz
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) constitutes life-threatening autoimmune diseases affecting every organ, including the kidneys, where they cause necrotizing crescentic glomerulonephritis. ANCA activates neutrophils and activated neutrophils damage the endothelium, leading to vascular inflammation and necrosis. Better understanding of neutrophil-mediated AAV disease mechanisms may reveal novel treatment strategies. Here we report that ANCA induces neutrophil extracellular traps (NETs) via receptor-interacting protein kinase (RIPK) 1/3- and mixed-lineage kinase domain-like (MLKL)-dependent necroptosis...
October 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29069574/extracellular-trap-like-fiber-release-may-not-be-a-prominent-defence-response-in-snails-evidence-from-three-species-of-freshwater-gastropod-molluscs
#15
Vladimír Skála, Anthony J Walker, Petr Horák
The discovery that mammalian neutrophils generate extracellular chromatin fibers that entrap/kill bacteria supported a new paradigm for innate immunity in animals. Similar findings in other models across diverse taxa have led to the hypothesis that the phenomenon is ancient and evolutionary conserved. Here, using a variety of synthetic (e.g. peptidoglycan) and biological (e.g. trematode larvae) components to investigate extracellular trap-like (ET-like) fiber production in vitro by haemocytes of Lymnaea stagnalis, Radix lagotis and Planorbarius corneus snails, ET-like fibers were rarely observed...
October 22, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/29061334/neutrophil-peptidyl-arginine-deiminase-4-has-a-pivotal-role-in-ischemia-reperfusion-induced-acute%C3%A2-kidney-injury
#16
Wesley M Raup-Konsavage, Yanming Wang, Wei Wei Wang, Denis Feliers, Hong Ruan, W Brian Reeves
Ischemia/reperfusion is a common cause of acute kidney injury (AKI). However, mechanisms underlying the sudden loss in kidney function and tissue injury remain to be fully elucidated. Here, we investigated the role of peptidyl arginine deiminase-4 (PAD4), which converts arginine to citrulline and plays a role in epigenetic regulation and inflammation, in renal ischemia/reperfusion injury. PAD4 expression was highly induced in infiltrating leukocytes 24 hours following renal ischemia and reperfusion. This induction was accompanied by citrullination of histone H3 and formation of neutrophil extracellular traps in kidneys of wild-type mice...
October 20, 2017: Kidney International
https://www.readbyqxmd.com/read/29059399/con-high-volume-plasma-exchange-application-in-nephrology-and-beyond
#17
Wladimir Szpirt, Joseph Schwartz
The rationale behind the use of plasma exchange (PE) includes the removal of autoantibodies and other plasma constituents, such as cytokines, complement components, neutrophil extracellular traps, and microparticles, and the substitution of missing plasma factors. The more established indications are associated with the beneficial effects of PE of reducing the plasma levels of pathogenic agents, although the efficiency of this process decreases during the course of the procedure as the substituted replacement fluid dilutes the patient's original plasma...
September 1, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29053025/e-cigarette-use-causes-a-unique-innate-immune-response-in-the-lung-involving-increased-neutrophilic-activation-and-altered-mucin-secretion
#18
Boris Reidel, Giorgia Radicioni, Phillip Clapp, Amina A Ford, Sabri Abdelwahab, Meghan E Rebuli, Prashamsha Haridass, Neil E Alexis, Ilona Jaspers, Mehmet Kesimer
RATIONALE: E-cigarettes have become increasingly popular and little is known about their potential adverse health effects. OBJECTIVE: To determine the effects of e-cigarette use on the airways. METHODS: Induced sputum samples from cigarette smokers, e-cigarette users, and non-smokers, were analyzed by quantitative proteomics, and the total and individual concentrations of mucins MUC5AC and MUC5B were determined by light scattering/refractometry and labeled mass spectrometry, respectively...
October 20, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/29052682/probing-blood-cell-mechanics-of-hematologic-processes-at-the-single-micron-level
#19
Jordan C Ciciliano, Reza Abbaspour, Julia Woodall, Caroline Wu, Muhannad S Bakir, Wilbur A Lam
Blood cells circulate in a dynamic fluidic environment, and during hematologic processes such as hemostasis, thrombosis, and inflammation, blood cells interact biophysically with a myriad of vascular matrices-blood clots and the subendothelial matrix. While it is known that adherent cells physiologically respond to the mechanical properties of their underlying matrices, how blood cells interact with their mechanical microenvironment of vascular matrices remains poorly understood. To that end, we developed microfluidic systems that achieve high fidelity, high resolution, single-micron PDMS features that mimic the physical geometries of vascular matrices...
November 7, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/29052524/soluble-cd40l-is-associated-with-increased-oxidative-burst-and-neutrophil-extracellular-trap-release-in-beh%C3%A3-et-s-disease
#20
Sandro Félix Perazzio, Paulo Vitor Soeiro-Pereira, Viviane Cardoso Dos Santos, Marlon Vilela de Brito, Bruno Salu, Maria Luiza Vilela Oliva, Anne Margherite Stevens, Alexandre Wagner Silva de Souza, Hans D Ochs, Troy R Torgerson, Antonio Condino-Neto, Luis Eduardo Coelho Andrade
BACKGROUND: Studies have suggested that soluble factors in plasma from patients with active (aBD) and inactive (iBD) Behçet's disease (BD) stimulate neutrophil function. Soluble CD40 ligand (sCD40L) is an important mediator of inflammation in BD. Its expression and effect on neutrophil oxidative burst and neutrophil extracellular trap (NET) release have not been characterized. In this study, we sought to investigate the role of plasma and the CD40L pathway on NET release and the oxidative burst profile in patients with aBD and iBD...
October 19, 2017: Arthritis Research & Therapy
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