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https://www.readbyqxmd.com/read/29472233/novel-role-of-il-interleukin-1%C3%AE-in-neutrophil-extracellular-trap-formation-and-abdominal-aortic-aneurysms
#1
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
https://www.readbyqxmd.com/read/29462936/new-insights-into-the-immune-molecular-regulation-of-the-pathogenesis-of-acute-respiratory-distress-syndrome
#2
REVIEW
Chin-Yao Yang, Chien-Sheng Chen, Giou-Teng Yiang, Yeung-Leung Cheng, Su-Boon Yong, Meng-Yu Wu, Chia-Jung Li
Acute respiratory distress syndrome is an inflammatory disease characterized by dysfunction of pulmonary epithelial and capillary endothelial cells, infiltration of alveolar macrophages and neutrophils, cell apoptosis, necroptosis, NETosis, and fibrosis. Inflammatory responses have key effects on every phase of acute respiratory distress syndrome. The severe inflammatory cascades impaired the regulation of vascular endothelial barrier and vascular permeability. Therefore, understanding the relationship between the molecular regulation of immune cells and the pulmonary microenvironment is critical for disease management...
February 16, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29459871/-staphylococcal-protein-a-is-a-key-factor-in-neutrophil-extracellular-traps-formation
#3
Tamara Hoppenbrouwers, Andi R Sultan, Tsion E Abraham, Nicole A Lemmens-den Toom, Silvie Hansenová Maňásková, Wiggert A van Cappellen, Adriaan B Houtsmuller, Willem J B van Wamel, Moniek P M de Maat, Johan W van Neck
Staphylococcus aureus are strong inducers of neutrophil extracellular traps (NETs), a defense mechanism of neutrophils against pathogens. Our aim was to explore the role of Protein A in S. aureus -induced NETosis. We determined the Protein A production of four different S. aureus strains and found a direct relationship between the degree of NETosis induction and Protein A production: strains producing higher concentrations of Protein A evoke significantly more NETs. A S. aureus strain in which Protein A as well as a second binding protein for immunoglobulins ( Sbi ) have been knocked-out (Δ SpA Δ Sbi ) induced significantly less NETosis than the wild-type strain...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29447842/neutrophils-drive-type-i-interferon-production-and-autoantibodies-in-wiskott-aldrich-syndrome
#4
K E Cervantes-Luevano, N Caronni, M C Castiello, E Fontana, G Piperno, A Naseem, P Uva, M Bosticardo, G E Marcovecchio, L D Notarangelo, M P Cicalese, A Aiuti, A Villa, F Benvenuti
BACKGROUND: Wiskott-Aldrich syndrome (WAS) is a rare primary immunodeficiency caused by mutations in WASp, a key regulator of cytoskeletal dynamics in hematopoietic cells. A high proportion of patients develop autoimmunity due to a breakdown in T and B cell tolerance. Moreover, excessive production of type-I interferon by plasmacytoid DCs contribute to autoimmune signs, however, the factors that triggers excessive innate activation have not been defined. OBJECTIVE: Neutrophils extracellular traps (NETs) emerged as major initiating factors in diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA)...
February 12, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29439290/cell-death-nucleic-acids-and-immunity-inflammation-beyond-the-grave
#5
REVIEW
Keith B Elkon
Cells of the innate immune system are rigged with sensors that detect nucleic acids derived from microbes, especially viruses. It has become clear that these same sensors that respond to nucleic acids derived from damaged cells or defective intracellular processing are implicated in triggering diseases such as lupus and arthritis. The ways in which cells die and the concomitant presence of proteins and peptides that allow nucleic acids to re-enter cells profoundly influence innate immune responses. This review briefly discusses different types of programmed necrosis such as pyroptosis, necroptosis and NETosis and explains how nucleic acids can engage intracellular receptors and stimulate inflammation...
February 13, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29438164/the-autoimmune-ecology-an-update
#6
Juan-Manuel Anaya, Paula Restrepo-Jiménez, Carolina Ramírez-Santana
PURPOSE OF REVIEW: The autoimmune ecology refers to the interactions between individuals and their environment leading to a breakdown in immune tolerance and, therefore, to the development of one or more autoimmune diseases in such an individual. Herein, an update is offered on four specific factors associated with autoimmune diseases, namely, vitamin D, smoking, alcohol and coffee consumption from the perspective of exposome and metabolomics. RECENT FINDINGS: Smoking is associated with an increased risk for most of the autoimmune diseases...
February 12, 2018: Current Opinion in Rheumatology
https://www.readbyqxmd.com/read/29437577/mir-146a-regulates-neutrophil-extracellular-trap-formation-that-predicts-adverse-cardiovascular-events-in-patients-with-atrial-fibrillation
#7
Ana B Arroyo, Asunción M de Los Reyes-García, José Miguel Rivera-Caravaca, Patricia Valledor, Nuria García-Barberá, Vanessa Roldán, Vicente Vicente, Constantino Martínez, Rocio González-Conejero
OBJECTIVE: Atrial fibrillation (AF) patients experience adverse cardiovascular events (ACEs) despite anticoagulant therapy. We reported that rs2431697 of miR-146a, a negative regulator of inflammation, predicts ACEs in patients with AF. The relationship between neutrophil extracellular traps and thrombogenesis is known. Thus, our aim was to evaluate the role of neutrophil extracellular trap compounds as prognostic markers of ACEs in AF and to study whether miR-146a affects NETosis. APPROACH AND RESULTS: We included 336 steadily anticoagulated AF patients with a median follow-up of 7...
February 8, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29425807/inhibition-of-echis-carinatus-venom-by-dna-a-promising-therapeutic-molecule-for-snakebite-management
#8
Basavarajaiah Swethakumar, Somanathapura K NaveenKumar, Gajanan D Katkar, Kesturu S Girish, Kempaiah Kemparaju
BACKGROUND: E. carinatus bite is a serious threat to South-Asian countries including India, as it causes the highest number of deaths and debilitating sustained tissue necrosis at the bite site. One of our previous studies has demonstrated the strong interaction between DNA and E. carinatus venom. Therefore, in this study, the effect of DNA on E. carinatus venom has been examined. METHODS: Here we show that calf thymus DNA interact strongly with E. carinatus venom and inhibits its enzymatic and pharmacological activities such as proteolytic, hemolytic, hyaluronidase, L-amino acid oxidase, NETosis, hemorrhage, pro-coagulant, and lethality...
February 6, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29376892/factor-xii-and-upar-upregulate-neutrophil-functions-to-influence-wound-healing
#9
Evi X Stavrou, Chao Fang, Kara L Bane, Andy T Long, Clément Naudin, Erdem Kucukal, Agharnan Gandhi, Adina Brett-Morris, Michele M Mumaw, Sudeh Izadmehr, Alona Merkulova, Cindy C Reynolds, Omar Alhalabi, Lalitha Nayak, Wen-Mei Yu, Cheng-Kui Qu, Howard J Meyerson, George R Dubyak, Umut A Gurkan, Marvin T Nieman, Anirban Sen Gupta, Thomas Renné, Alvin H Schmaier
Coagulation factor XII (FXII) deficiency is associated with decreased neutrophil migration, but the mechanisms remain uncharacterized. Here, we examine how FXII contributes to the inflammatory response. In 2 models of sterile inflammation, FXII-deficient mice (F12-/-) had fewer neutrophils recruited than WT mice. We discovered that neutrophils produced a pool of FXII that is functionally distinct from hepatic-derived FXII and contributes to neutrophil trafficking at sites of inflammation. FXII signals in neutrophils through urokinase plasminogen activator receptor-mediated (uPAR-mediated) Akt2 phosphorylation at S474 (pAktS474)...
January 29, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29376324/turning-the-spotlight-on-lipids-in-non-apoptotic-cell-death
#10
Laura R Parisi, Lauren M Morrow, Michelle B Visser, G Ekin Atilla-Gokcumen
Although apoptosis has long dominated the spotlight, studies in the last two decades have expanded the repertoire of programmed cell death (PCD). Several forms of non-apoptotic regulated cell death have been identified, with important links to organismal homeostasis and different disease pathologies. Necroptosis, ferroptosis, pyroptosis and NETosis are the major forms of PCD that have attracted attention. Clear biochemical distinctions differentiate these forms of non-apoptotic PCD at the protein and membrane levels...
January 27, 2018: ACS Chemical Biology
https://www.readbyqxmd.com/read/29367211/monosodium-urate-crystals-generate-nuclease-resistant-neutrophil-extracellular-traps-via-a-distinct-molecular-pathway
#11
Simon M Chatfield, Kathrin Grebe, Lachlan W Whitehead, Kelly L Rogers, Thomas Nebl, James M Murphy, Ian P Wicks
Neutrophil extracellular traps (NETs) and the cell death associated with it (NETosis) have been implicated in numerous diseases. Mechanistic studies of NETosis have typically relied on nonphysiological stimuli, such as PMA. The human disease of gout is caused by monosodium urate (MSU) crystals. We observed that DNA consistent with NETs is present in fluid from acutely inflamed joints of gout patients. NETs also coat the crystals found in uninflamed tophi of chronic gout patients. We developed a quantitative, live cell imaging assay, which measures the key features of NETosis, namely, cell death and chromatin decondensation...
January 24, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29324871/citrullinated-histone-h3-as-a-novel-prognostic-blood-marker-in-patients-with-advanced-cancer
#12
Charlotte Thålin, Staffan Lundström, Cedric Seignez, Maud Daleskog, Annika Lundström, Peter Henriksson, Thomas Helleday, Mia Phillipson, Håkan Wallén, Mélanie Demers
Citrullinated histone H3 (H3Cit) is a central player in the neutrophil release of nuclear chromatin, known as neutrophil extracellular traps (NETs). NETs have been shown to elicit harmful effects on the host, and were recently proposed to promote tumor progression and spread. Here we report significant elevations of plasma H3Cit in patients with advanced cancer compared with age-matched healthy individuals. These elevations were specific to cancer patients as no increase was observed in severely ill and hospitalized patients with a higher non-malignant comorbidity...
2018: PloS One
https://www.readbyqxmd.com/read/29304522/the-pathophysiological-role-of-neutrophil-extracellular-traps-in-inflammatory-diseases
#13
Aldo Bonaventura, Luca Liberale, Federico Carbone, Alessandra Vecchié, Candela Diaz-Cañestro, Giovanni G Camici, Fabrizio Montecucco, Franco Dallegri
Neutrophil pathogen-killing mechanism termed neutrophil extracellular traps (NETs) has been recently identified. NETs consist of chromatin and histones along with serine proteases and myeloperoxidase and are induced by a great variety of infectious and non-infectious stimuli . NETosis is a kind of programmed neutrophil death characterized by chromatin decondensation and release of nuclear granular contents, mainly driven by peptidylarginine deiminase 4 citrullination of histones. Although classically related to the protection against infectious pathogens, nowadays NETs have been described as a player of several pathophysiological processes...
January 2018: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/29236713/sirt3-deficiency-does-not-affect-venous-thrombosis-or-netosis-despite-mild-elevation-of-intracellular-ros-in-platelets-and-neutrophils-in-mice
#14
Hideki Hayashi, Deya Cherpokova, Kimberly Martinod, Thilo Witsch, Siu Ling Wong, Maureen Gallant, Stephen M Cifuni, Leonard P Guarente, Denisa D Wagner
Inflammation is a common denominator in chronic diseases of aging. Yet, how inflammation fuels these diseases remains unknown. Neutrophils are the primary leukocytes involved in the early phase of innate immunity and inflammation. As part of their anti-microbial defense, neutrophils form extracellular traps (NETs) by releasing decondensed chromatin lined with cytotoxic proteins. NETs have been shown to induce tissue injury and thrombosis. Here, we demonstrated that Sirt3, a nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase, an enzyme linked to human longevity, was expressed in mouse neutrophils and platelets...
2017: PloS One
https://www.readbyqxmd.com/read/29234042/cfdna-correlates-with-endothelial-damage-after-cardiac-surgery-with-prolonged-cardiopulmonary-bypass-and-amplifies-netosis-in-an-intracellular-tlr9-independent-manner
#15
Adnana Paunel-Görgülü, Max Wacker, Mouhamed El Aita, Shoreshfan Hassan, Georg Schlachtenberger, Antje Deppe, Yeong-Hoon Choi, Elmar Kuhn, Thorsten O Mehler, Thorsten Wahlers
Cardiopulmonary bypass (CPB) provokes inflammation culminating in organ dysfunction and increased mortality. Recently, neutrophil extracellular traps (NETs) have been found to be involved in a variety of cardiovascular diseases promoting tissue and organ injury. Here, we aimed to elaborate the proinflammatory potential of circulating cell-free (cf)DNA in patients undergoing cardiac surgery with CPB. Plasma was collected pre- and postoperatively as well as at d1, d3, d5 and d8 after surgery. At d1, we found circulating cfDNA levels to be significantly increased in patients with prolonged CPB duration (>100 min) when compared to those with shorter CPB times (CPB < 100 min)...
December 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29222696/thrombomodulin-favors-leukocyte-microvesicle-fibrinolytic-activity-reduces-netosis-and-prevents-septic-shock-induced-coagulopathy-in-rats
#16
Julie Helms, Raphaël Clere-Jehl, Elsa Bianchini, Pierrick Le Borgne, Mélanie Burban, Fatiha Zobairi, Jean-Luc Diehl, Lelia Grunebaum, Florence Toti, Ferhat Meziani, Delphine Borgel
BACKGROUND: Septic shock-induced disseminated intravascular coagulation is responsible for increased occurrence of multiple organ dysfunction and mortality. Immunothrombosis-induced coagulopathy may contribute to hypercoagulability. We aimed at determining whether recombinant human thrombomodulin (rhTM) could control exaggerated immunothrombosis by studying procoagulant responses, fibrinolysis activity borne by microvesicles (MVs) and NETosis in septic shock. METHODS: In a septic shock model after a cecal ligation and puncture-induced peritonitis (H0), rats were treated with rhTM or a placebo at H18, resuscitated and monitored during 4 h...
December 8, 2017: Annals of Intensive Care
https://www.readbyqxmd.com/read/29214674/neutrophil-extracellular-traps-in-plasma-from-dogs-with-immune-mediated-hemolytic-anemia
#17
C Lawson, S A Smith, M O'Brien, M McMichael
BACKGROUND: Neutrophil extracellular traps (NETs) are part of the innate immune response and are essential in local pathogen control, but are associated with pathological inflammation, organ damage, autoimmunity, and thrombosis. Immune-mediated hemolytic anemia (IMHA) is a pro-inflammatory, prothrombotic disease associated with high mortality. HYPOTHESIS/OBJECTIVES: Neutrophil extracellular traps (NETs) are a feature of the inflammatory process in dogs with IMHA...
December 7, 2017: Journal of Veterinary Internal Medicine
https://www.readbyqxmd.com/read/29196457/a-high-throughput-real-time-imaging-technique-to-quantify-netosis-and-distinguish-mechanisms-of-cell-death-in-human-neutrophils
#18
Sarthak Gupta, Diana W Chan, Kristien J Zaal, Mariana J Kaplan
Neutrophils play a key role in host defenses and have recently been implicated in the pathogenesis of autoimmune diseases by various mechanisms, including formation of neutrophil extracellular traps through a recently described distinct form of programmed cell death called NETosis. Techniques to assess and quantitate NETosis in an unbiased, reproducible, and efficient way are lacking, considerably limiting the advancement of research in this field. We optimized and validated, a new method to automatically quantify the percentage of neutrophils undergoing NETosis in real time using the IncuCyte ZOOM imaging platform and the membrane-permeability properties of two DNA dyes...
December 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29178989/interaction-of-factor-vii-activating-protease-fsap-with-neutrophil-extracellular-traps-nets
#19
Simona Grasso, Ariane Neumann, Irene M Lang, Michael Etscheid, Maren von Köckritz-Blickwede, Sandip M Kanse
The circulating zymogen form of Factor VII activating protease (FSAP) can be activated by histones and nucleosomes in vivo. These cell-death-associated nuclear factors are also actively extruded into the extracellular space by neutrophils through a process called neutrophil extracellular trap (NET) formation (NETosis). NETs are thought to be involved in host defense, inflammation as well as thrombosis. We have investigated the bidirectional interactions of FSAP and NETs. Phorbol ester-mediated NET formation was marginally stimulated by FSAP...
November 21, 2017: Thrombosis Research
https://www.readbyqxmd.com/read/29168915/a-novel-microdevice-for-rapid-neutrophil-purification-and-phenotyping-in-type-2-diabetes-mellitus
#20
Hui Min Tay, Rinkoo Dalan, King Ho Holden Li, Bernhard O Boehm, Han Wei Hou
Neutrophil dysfunction is strongly linked to type 2 diabetes mellitus (T2DM) pathophysiology, but the prognostic potential of neutrophil biomarkers remains largely unexplored due to arduous leukocyte isolation methods. Herein, a novel integrated microdevice is reported for single-step neutrophil sorting and phenotyping (chemotaxis and formation of neutrophil extracellular traps (NETosis)) using small blood volumes (fingerprick). Untouched neutrophils are purified on-chip from whole blood directly using biomimetic cell margination and affinity-based capture, and are exposed to preloaded chemoattractant or NETosis stimulant to initiate chemotaxis or NETosis, respectively...
November 23, 2017: Small
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