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Neutrophil traps

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https://www.readbyqxmd.com/read/29161586/re-cyclin-cell-cycle-components-to-make-nets
#1
Jean Albrengues, Robert W Wysocki, Laura Maiorino, Mikala Egeblad
Neutrophil extracellular traps (NETs) are critical for the clearance of large pathogens and are also implicated in thrombosis, autoimmunity, and cancer. In this issue of Developmental Cell, Amulic et al. (2017) show that the terminally differentiated, non-cycling neutrophils repurpose cell-cycle proteins and pathways to form NETs.
November 20, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29158081/streptococcus-pyogenes-nuclease-a-spna-mediated-virulence-does-not-exclusively-depend-on-nuclease-activity
#2
Callum Chalmers, Adrina Hema J Khemlani, Chae Ryeong Sohn, Jacelyn Mei San Loh, Catherine Jia-Yun Tsai, Thomas Proft
BACKGROUND: Streptococcus pyogenes, or Group A Streptococcus (GAS), is a human pathogen that causes a wide range of diseases, including pharyngitis, necrotizing fasciitis and toxic shock syndrome. The bacterium produces a large arsenal of virulence factors, including the cell wall-anchored Streptococcus pyogenes nuclease A (SpnA), which facilitates immune evasion by degrading the DNA backbone of neutrophil extracellular traps. SpnA consists of a C-terminal endo/exonuclease domain and a N-terminal domain of unknown function...
November 13, 2017: Journal of Microbiology, Immunology, and Infection, Wei Mian Yu Gan Ran za Zhi
https://www.readbyqxmd.com/read/29156107/hemodynamic-force-triggers-rapid-netosis-within-sterile-thrombotic-occlusions
#3
X Yu, J Tan, S L Diamond
BACKGROUND: Neutrophil extracellular traps (NETs) are released when neutrophils encounter infectious pathogens, especially during sepsis. Additionally, NETosis occurs during venous and arterial thrombosis, disseminated intravascular coagulation, and trauma. OBJECTIVE: We tested if hemodynamic forces trigger NETosis during sterile thrombosis. METHODS: NETs were imaged with Sytox-green during microfluidic perfusion of Factor XIIa-inhibited or thrombin-inhibited human whole blood over fibrillar collagen (± tissue factor)...
November 20, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29155721/visualizing-macrophage-extracellular-traps-using-confocal-microscopy
#4
Roleen Sharma, Kim M O'Sullivan, Stephen R Holdsworth, Philip G Bardin, Paul T King
A primary method used to define the presence of neutrophil extracellular traps (NETs) is confocal microscopy. We have modified established confocal microscopy methods to visualize macrophage extracellular traps (METs). These extracellular traps are defined by the presence of extracellular chromatin with co-expression of other components such as granule proteases, citrullinated histones, and peptidyl arginase deiminase (PAD). The expression of METs is generally measured after exposure to a stimulus and compared to un-stimulated samples...
October 19, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29155217/neutrophil-elastase-in-the-tumor-microenvironment
#5
Irina Lerman, Stephen R Hammes
Myeloid cell production within the bone marrow is accelerated in the setting of cancer, and the numbers of circulating and infiltrating neutrophils and granulocytic myeloid derived suppressor cells (MDSCs) correlate with tumor progression and patient survival. Cancer is therefore able to hijack the normally host-protective immune system and use it to further fuel growth and metastasis. Myeloid cells secrete neutrophil elastase and neutrophil extracellular traps (NETs) in response to cues within the tumor microenvironment, thereby leading to enhanced activity in a variety of cancer types...
November 16, 2017: Steroids
https://www.readbyqxmd.com/read/29155101/type-i-ifn-related-netosis-in-ataxia-telangiectasia-and-artemis-deficiency
#6
Ersin Gul, Esra Hazar Sayar, Bilgi Gungor, Fehime Kara Eroglu, Naz Surucu, Sevgi Keles, Sukru Nail Guner, Sıddıka Fındık, Esin Alpdündar, Ihsan Cihan Ayanoglu, Basak Kayaoglu, Busra Nur Geçkin, Hatice Asena Sanli, Tamer Kahraman, Cengiz Yakicier, Meltem Muftuoglu, Berna Oguz, Deniz Nazire Cagdas Ayvaz, Ihsan Gursel, Seza Ozen, Ismail Reisli, Mayda Gursel
BACKGROUND: Pathological inflammatory syndromes of unknown etiology are commonly observed in Ataxia telangiectasia (AT) and Artemis deficiency. Similar inflammatory manifestations also exist in STING-associated vasculopathy in infancy (SAVI) patients. OBJECTIVE: To test the hypothesis that the inflammation associated manifestations observed in AT and Artemis deficient patients stem from increased type I IFN signature leading to neutrophil mediated pathological damage...
November 15, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29150539/ros-and-glutathionylation-balance-cytoskeletal-dynamics-in-neutrophil-extracellular-trap-formation
#7
Darko Stojkov, Poorya Amini, Kevin Oberson, Christiane Sokollik, Andrea Duppenthaler, Hans-Uwe Simon, Shida Yousefi
The antimicrobial defense activity of neutrophils partly depends on their ability to form neutrophil extracellular traps (NETs), but the underlying mechanism controlling NET formation remains unclear. We demonstrate that inhibiting cytoskeletal dynamics with pharmacological agents or by genetic manipulation prevents the degranulation of neutrophils and mitochondrial DNA release required for NET formation. Wiskott-Aldrich syndrome protein-deficient neutrophils are unable to polymerize actin and exhibit a block in both degranulation and DNA release...
November 17, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/29133856/therapeutic-targeting-of-extracellular-dna-improves-the-outcome-of-intestinal-ischemic-reperfusion-injury-in-neonatal-rats
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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)...
November 20, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29102925/role-for-neutrophil-extracellular-traps-nets-and-platelet-aggregation-in-early-sepsis-induced-hepatic-dysfunction
#17
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
#18
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
#19
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
#20
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
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