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https://www.readbyqxmd.com/read/28536276/persistent-immune-stimulation-exacerbates-genetically-driven-myeloproliferative-disorders-via-stromal-remodeling
#1
Claudio Tripodo, Alessia Burocchi, Pier Paolo Piccaluga, Claudia Chiodoni, Paola Portararo, Barbara Cappetti, Laura Botti, Alessandro Gulino, Alessandro Isidori, Arcangelo Liso, Giuseppe Visani, Maria Paola Martelli, Brunangelo Falini, Pier Paolo Pandolfi, Mario P Colombo, Sabina Sangaletti
Systemic immune stimulation has been associated with increased risk of myeloid malignancies, but the pathogenic link is unknown. We demonstrate in animal models that experimental systemic immune activation alters the bone marrow stromal microenvironment, disarranging extracellular matrix (ECM) microarchitecture, with down-regulation of SPARC and collagen-I and induction of complement activation. These changes were accompanied by a decrease in Treg frequency and by an increase in activated effector T cells. Under these conditions, hematopoietic precursors harboring nucleophosmin-1 (NPM1) mutation generated myeloid cells unfit for normal hematopoiesis but prone to immunogenic death, leading to neutrophil extracellular trap (NET) formation...
May 23, 2017: Cancer Research
https://www.readbyqxmd.com/read/28487062/mitochondrial-damps-are-released-during-cardiopulmonary-bypass-surgery-and-are-associated-with-postoperative-atrial-fibrillation
#2
Nicola Sandler, Elzbieta Kaczmarek, Kiyoshi Itagaki, Yi Zheng, Leo Otterbein, Kamal Khabbaz, David Liu, Venkatachalam Senthilnathan, Russell L Gruen, Carl J Hauser
BACKGROUND: Atrial fibrillation (AF) is the most frequent complication of surgery performed on cardiopulmonary bypass (CPB) and recent work associates CPB with postoperative inflammation. We have shown that all tissue injury releases mitochondrial damage associated molecular patterns (mtDAMPs) including mitochondrial DNA (mtDNA). This can act as a direct, early activator of neutrophils (PMN), eliciting a systemic inflammatory response syndrome (SIRS) while suppressing PMN function. Neutrophil Extracellular Traps (NETs) are crucial to host defence...
March 24, 2017: Heart, Lung & Circulation
https://www.readbyqxmd.com/read/28486563/in-vitro-induction-of-netosis-comprehensive-live-imaging-comparison-and-systematic-review
#3
Tamara Hoppenbrouwers, Anouchska S A Autar, Andi R Sultan, Tsion E Abraham, Wiggert A van Cappellen, Adriaan B Houtsmuller, Willem J B van Wamel, Heleen M M van Beusekom, Johan W van Neck, Moniek P M de Maat
BACKGROUND: Multiple inducers of in vitro Neutrophil Extracellular Trap (NET) formation (NETosis) have been described. Since there is much variation in study design and results, our aim was to create a systematic review of NETosis inducers and perform a standardized in vitro study of NETosis inducers important in (cardiac) wound healing. METHODS: In vitro NETosis was studied by incubating neutrophils with PMA, living and dead bacteria (S. aureus and E. coli), LPS, (activated) platelets (supernatant), glucose and calcium ionophore Ionomycin using 3-hour periods of time-lapse confocal imaging...
2017: PloS One
https://www.readbyqxmd.com/read/28467984/neutrophil-extracellular-traps-stimulate-proinflammatory-responses-in-human-airway-epithelial-cells
#4
Florencia Sabbione, Irene A Keitelman, Leonardo Iula, Mariana Ferrero, Mirta N Giordano, Pablo Baldi, Martín Rumbo, Carolina Jancic, Analía S Trevani
Tissue injury leads to the release of uric acid (UA). At high local concentrations, UA can form monosodium urate crystals (MSU). MSU and UA stimulate neutrophils to release extracellular traps (NET). Here, we investigated whether these NET could be involved in the development of inflammation by stimulating cytokine release by airway epithelial cells. We found that NET significantly increased the secretion of CXCL8/IL-8 and IL-6 by alveolar and bronchial epithelial cells. These effects were not observed when NETosis was inhibited by Diphenyleneiodonium, elastase inhibitor, or Cl-amidine...
May 4, 2017: Journal of Innate Immunity
https://www.readbyqxmd.com/read/28465447/human-blood-monocytes-are-able-to-form-extracellular-traps
#5
Vanessa Granger, Dorothée Faille, Vanessa Marani, Benoît Noël, Yann Gallais, Natacha Szely, Héloïse Flament, Marc Pallardy, Sylvie Chollet-Martin, Luc de Chaisemartin
Neutrophil extracellular traps (NETs) are extracellular DNA filaments formed during neutrophil activation. This process, called netosis, was originally associated with neutrophil antibacterial properties. However, several lines of evidence now suggest a major role for netosis in thrombosis, autoimmune diseases, and cancer. We demonstrate here that highly purified human blood monocytes are also capable of extracellular trap (ET) release in response to several stimuli. Monocyte ETs display a morphology analogous to NETs and are associated with myeloperoxidase (MPO), lactoferrin (LF), citrullinated histones, and elastase...
May 2, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28465139/diagnostic-potential-of-netosis-derived-products-for-disease-activity-atherosclerosis-and-therapeutic-effectiveness-in-rheumatoid-arthritis-patients
#6
C Pérez-Sánchez, P Ruiz-Limón, M A Aguirre, Y Jiménez-Gómez, I Arias-de la Rosa, M C Ábalos-Aguilera, A Rodriguez-Ariza, M C Castro-Villegas, R Ortega-Castro, P Segui, C Martinez, R Gonzalez-Conejero, S Rodríguez-López, J A Gonzalez-Reyes, J M Villalba, E Collantes-Estévez, A Escudero, N Barbarroja, Ch López-Pedrera
OBJECTIVES: 1) To assess the association of NETosis and NETosis-derived products with the activity of the disease and the development of cardiovascular disease in RA; 2) To evaluate the involvement of NETosis on the effects of biologic therapies such as anti-TNF alpha (Infliximab) and anti-IL6R drugs (Tocilizumab). METHODS: One hundred and six RA patients and 40 healthy donors were evaluated for the occurrence of NETosis. Carotid-intimae media thickness was analyzed as early atherosclerosis marker...
April 29, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28459437/host-dna-released-by-netosis-promotes-rhinovirus-induced-type-2-allergic-asthma-exacerbation
#7
Marie Toussaint, David J Jackson, Dawid Swieboda, Anabel Guedán, Theodora-Dorita Tsourouktsoglou, Yee Man Ching, Coraline Radermecker, Heidi Makrinioti, Julia Aniscenko, Michael R Edwards, Roberto Solari, Frédéric Farnir, Venizelos Papayannopoulos, Fabrice Bureau, Thomas Marichal, Sebastian L Johnston
Respiratory viral infections represent the most common cause of allergic asthma exacerbations. Amplification of the type-2 immune response is strongly implicated in asthma exacerbation, but how virus infection boosts type-2 responses is poorly understood. We report a significant correlation between the release of host double-stranded DNA (dsDNA) following rhinovirus infection and the exacerbation of type-2 allergic inflammation in humans. In a mouse model of allergic airway hypersensitivity, we show that rhinovirus infection triggers dsDNA release associated with the formation of neutrophil extracellular traps (NETs), known as NETosis...
May 1, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28420069/cathelicidin-ll-37-and-its-correlation-with-pro-oxidant-antioxidant-balance-and-disease-activity-in-systemic-lupus-erythematosus-a-cross-sectional-human-study
#8
M Sahebari, G Roshandel, N Saadati, M Saghafi, N Abdolahi, Z Rezaieyazdi
Background Cathelicidin (LL-37), an endogenous antimicrobial peptide, has recently been involved in the pathogenesis of autoimmune diseases. To assess whether LL-37 reflects disease activity, we measured serum levels of it in systemic lupus erythematosus (SLE) patients with active and inactive disease compared to healthy controls. LL-37 was also compared between new and old cases. Moreover, the correlation of LL-37 and pro-oxidant, antioxidant balance (PAB) was measured. Methods The study population consisted of 50 SLE patients and 28 healthy controls...
January 1, 2017: Lupus
https://www.readbyqxmd.com/read/28408624/activated-protein-c-inhibits-neutrophil-extracellular-trap-formation-in-vitro-and-activation-in-vivo
#9
Laura D Healy, Cristina Puy, José A Fernández, Annachiara Mitrugno, Ravi S Keshari, Nyiawung A Taku, Tiffany T Chu, Xiao Xu, András Gruber, Florea Lupu, John H Griffin, Owen J T McCarty
Activated protein C (APC) is a multi-functional serine protease with anticoagulant, cytoprotective, and anti-inflammatory activities. In addition to the cytoprotective effects of APC on endothelial cells, podocytes, and neurons, APC cleaves and detoxifies extracellular histones, a major component of neutrophil extracellular traps (NETs). NETs promote pathogen clearance but also can lead to thrombosis; the pathways that negatively regulate NETosis are largely unknown. Thus, we studied whether APC is capable of directly inhibiting NETosis via receptor-mediated cell signaling mechanisms...
April 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28382034/neutrophil-extracellular-traps-of-cynoglossus-semilaevis-production-characteristics-and-antibacterial-effect
#10
Ming-Li Zhao, Heng Chi, Li Sun
Neutrophil extracellular traps (NETs) are structures released by neutrophils as a cellular immune defense against microbial invasion. The process of NETs generation, netosis (NETosis), can take place via either a suicidal mechanism, during which the NETs-releasing cells became dead, or a "live" mechanism, during which the NETs-releasing cells remain vital. NETosis has been studied intensively in mammals in recent years, but very little is known about the NETosis in fish. In this study, we examined NETosis in tongue sole (Cynoglossus semilaevis), a species of teleost with important economic values...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28375544/aging-related-atg5-defect-impairs-neutrophil-extracellular-traps-formation
#11
Fengying Xu, Chengmi Zhang, Zui Zou, Erica Ky Fan, Linsong Chen, Yuehua Li, Timothy R Billiar, Mark A Wilson, Xueyin Shi, Jie Fan
Neutrophil extracellular traps (NETs) formation is an important function of the innate immune system against infections. It has been proven that aging dysregulates immunity and impairs neutrophil function. However, the influence of aging on the ability to produce NETs has yet to be fully addressed. In this study, we tested the hypothesis that a lower level of autophagy in neutrophils from aged mice was responsible for the decrease in NETs formation. We demonstrated that a broad range of Toll-like receptor 2 (TLR2) ligands could efficiently induce a reactive oxygen species (ROS)-dependent NETs release in young mice, but not in aged ones...
April 4, 2017: Immunology
https://www.readbyqxmd.com/read/28374518/neutrophil-extracellular-traps-can-serve-as-platforms-for-processing-and-activation-of-il-1-family-cytokines
#12
Danielle M Clancy, Conor M Henry, Graeme P Sullivan, Seamus J Martin
Activated neutrophils can undergo a mode of regulated cell death, called NETosis, that results in the extrusion of chromatin into the extracellular space, thereby acting as extracellular traps for microorganisms. Neutrophil-derived extracellular traps (NETs) are comprised of DNA decorated with histones, antimicrobial proteins and neutrophil granule proteases, such as elastase and cathepsin G (Cat G). NET-associated factors are thought to enhance the antimicrobial properties of these structures and localisation of antimicrobial molecules on NETs may serve to increase their local concentration...
April 4, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28370080/evaluation-of-assays-for-quantification-of-dna-in-canine-plasma-as-an-indirect-marker-of-netosis
#13
Stephanie A Smith, Corinne M Lawson, Maureen A McMichael, Katrina Jung, Mauria O'Brien, Ron Achiel
BACKGROUND: Neutrophil extracellular traps (NET), consisting of a filamentous DNA/chromatin-histone scaffold originating from neutrophils are part of the innate immune response, may be released under a variety of inflammatory conditions and are associated with an increased risk for thrombosis. OBJECTIVES: The purpose of this study was to evaluate a SYTOX green fluorescence assay and a histone-DNA complex (hisDNA) ELISA for quantification of NET-related DNA in canine plasma...
April 3, 2017: Veterinary Clinical Pathology
https://www.readbyqxmd.com/read/28362726/-hints-in-the-killer-protein-gasdermin-d-unveiling-the-secrets-of-gasdermins-driving-cell-death
#14
REVIEW
Shiqiao Qiu, Jing Liu, Feiyue Xing
Pyroptosis is a lytic form of cell death distinguished from apoptosis, ferroptosis, necrosis, necroptosis, NETosis, oncosis, pyronecrosis and autophagy. Proinflammatory caspases cleave a gasdermin D (GSDMD) protein to generate a 31 kDa N-terminal domain. The cleavage relieves the intramolecular inhibition on the gasdermin-N domain, which then moves to the plasma membrane to exhibit pore-forming activity. Thus, GSDMD acts as the final and direct executor of pyroptotic cell death. Owing to the selective targeting of the inner leaflet of the plasma membrane with the pore-forming that determines pyroptotic cell death, GSDMD could be a potential target to control cell death or extracellular bacterial infections...
April 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28356516/efficacy-long-term-toxicity-and-mechanistic-studies-of-gold-nanorods-photothermal-therapy-of-cancer-in-xenograft-mice
#15
Moustafa R K Ali, Mohammad Aminur Rahman, Yue Wu, Tiegang Han, Xianghong Peng, Megan A Mackey, Dongsheng Wang, Hyung Ju Shin, Zhuo G Chen, Haopeng Xiao, Ronghu Wu, Yan Tang, Dong M Shin, Mostafa A El-Sayed
Gold nanorods (AuNRs)-assisted plasmonic photothermal therapy (AuNRs-PPTT) is a promising strategy for combating cancer in which AuNRs absorb near-infrared light and convert it into heat, causing cell death mainly by apoptosis and/or necrosis. Developing a valid PPTT that induces cancer cell apoptosis and avoids necrosis in vivo and exploring its molecular mechanism of action is of great importance. Furthermore, assessment of the long-term fate of the AuNRs after treatment is critical for clinical use. We first optimized the size, surface modification [rifampicin (RF) conjugation], and concentration (2...
April 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28352169/evidence-of-eosinophil-extracellular-trap-cell-death-in-copd-does-it-represent-the-trigger-that-switches-on-the-disease
#16
Loli Uribe Echevarría, Carolina Leimgruber, Jorge García González, Alberto Nevado, Ruth Álvarez, Luciana N García, Amado A Quintar, Cristina A Maldonado
In spite of the numerous studies on chronic obstructive pulmonary disease (COPD), the cellular and molecular basis of the disease's development remain unclear. Neutrophils and eosinophils are known to be key players in COPD. Recently, neutrophil extracellular trap cell death (NETosis), a mechanism due to decondensation and extrusion of chromatin to form extracellular traps, has been demonstrated in COPD. However, there is limited knowledge about eosinophil extracellular trap cell death (EETosis) and its role in the pathogenesis of COPD...
2017: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/28350058/neutrophil-extracellular-traps-induce-il-1%C3%AE-production-by-macrophages-in-combination-with-lipopolysaccharide
#17
Zhongshuang Hu, Taisuke Murakami, Hiroshi Tamura, Johannes Reich, Kyoko Kuwahara-Arai, Toshiaki Iba, Yoko Tabe, Isao Nagaoka
Upon exposure to invading microorganisms, neutrophils undergo NETosis, a recently identified type of programmed cell death, and release neutrophil extracellular traps (NETs). NETs are described as an antimicrobial mechanism, based on the fact that NETs can trap microorganisms and exhibit bactericidal activity through the action of NET‑associated components. In contrast, the components of NETs have been recognized as damage‑associated molecular pattern molecules (DAMPs), which trigger inflammatory signals to induce cell death, inflammation and organ failure...
January 27, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28337204/phenol-soluble-modulin-%C3%AE-peptide-toxins-from-aggressive-staphylococcus-aureus-induce-rapid-formation-of-neutrophil-extracellular-traps-through-a-reactive-oxygen-species-independent-pathway
#18
Halla Björnsdottir, Agnes Dahlstrand Rudin, Felix P Klose, Jonas Elmwall, Amanda Welin, Marios Stylianou, Karin Christenson, Constantin F Urban, Huamei Forsman, Claes Dahlgren, Anna Karlsson, Johan Bylund
Neutrophils have the ability to capture and kill microbes extracellularly through the formation of neutrophil extracellular traps (NETs). These are DNA and protein structures that neutrophils release extracellularly and are believed to function as a defense mechanism against microbes. The classic NET formation process, triggered by, e.g., bacteria, fungi, or by direct stimulation of protein kinase C through phorbol myristate acetate, is an active process that takes several hours and relies on the production of reactive oxygen species (ROS) that are further modified by myeloperoxidase (MPO)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28303140/netosis-in-alzheimer-s-disease
#19
REVIEW
Enrica Caterina Pietronigro, Vittorina Della Bianca, Elena Zenaro, Gabriela Constantin
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the progressive deterioration of cognitive functions. Its neuropathological features include amyloid-β (Aβ) accumulation, the formation of neurofibrillary tangles, and the loss of neurons and synapses. Neuroinflammation is a well-established feature of AD pathogenesis, and a better understanding of its mechanisms could facilitate the development of new therapeutic approaches. Recent studies in transgenic mouse models of AD have shown that neutrophils adhere to blood vessels and migrate inside the parenchyma...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28293240/extracellular-acidification-inhibits-the-ros-dependent-formation-of-neutrophil-extracellular-traps
#20
Martina Behnen, Sonja Möller, Antonia Brozek, Matthias Klinger, Tamás Laskay
The inflammatory microenvironment is commonly characterized by extracellular acidosis (pH < 7.35). Sensitivity to pH, CO2 or bicarbonate concentrations allows neutrophils to react to changes in their environment and to detect inflamed areas in the tissue. One important antimicrobial effector mechanism is the production of neutrophil extracellular traps (NETs), which are released during a programmed reactive oxygen species (ROS)-dependent cell death, the so-called NETosis. Although several functions of neutrophils have been analyzed under acidic conditions, the effect of extracellular acidosis on NETosis remains mainly unexplored and the available experimental results are contradictory...
2017: Frontiers in Immunology
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