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Sachin David, Vikram Mathews
Acute promyelocytic leukemia (APL) is a subtype of leukemia which is associated with unique and distinctive coagulopathy. In the absence of treatment it is rapidly fatal and even after initiation of therapy the major cause of early mortality is related to hemorrhagic complications. The coagulopathy can be exacerbated with the start of treatment. In the absence of early hemorrhage related deaths the probability of cure exceeds 90% in low and intermediate risk patients and 80% even in high risk patients, highlighting the importance of understanding the pathophysiology of this complication and instituting prompt and appropriate management strategies...
April 2018: Thrombosis Research
M T C Nascimento, K P Silva, M C F Garcia, M N Medeiros, E A Machado, S B Nascimento, E M Saraiva
Extracellular traps (ETs), web-like structures composed of DNA and histones, are released by innate immune cells in a wide range of organisms. ETs capture microorganisms, thereby avoiding their spread, and also concentrate antimicrobial molecules, which helps to kill microbes. Although vertebrate innate immune systems share homology with the insect immune system, ETosis have yet to be characterized in insects. Here, we report that the hemocytes of the hemimetabolous insect Periplaneta americana release ETs upon in vitro stimulation...
July 2018: Developmental and Comparative Immunology
Tao Li, Ruishuang Ma, Yan Zhang, Hongdan Mo, Xiaoyan Yang, Shaoshan Hu, Lixiu Wang, Valerie A Novakovic, He Chen, Junjie Kou, Yayan Bi, Bo Yu, Shaohong Fang, Jinghua Wang, Jin Zhou, Jialan Shi
Despite the high efficacy and safety of arsenic trioxide (ATO) in treating acute promyelocytic leukemia (APL) and eradicating APL leukemia-initiating cells (LICs), the mechanism underlying its selective cytotoxicity remains elusive. We have recently demonstrated that APL cells undergo a novel cell death program, termed ETosis, through autophagy. However, the role of ETosis in ATO-induced APL LIC eradication remains unclear. For this study, we evaluated the effects of ATO on ETosis and the contributions of drug-induced ETosis to APL LIC eradication...
January 23, 2018: Cell Death & Disease
Yoshiaki Iwase, Yoji Horie, Yusuke Daiko, Sawao Honda, Yuji Iwamoto
A novel polyethoxysilsesquiazane ([EtOSi(NH)1.5 ]n , EtOSZ) was synthesized by ammonolysis at -78 °C of ethoxytrichlorosilane (EtOSiCl₃), which was isolated by distillation as a reaction product of SiCl₄ and EtOH. Attenuated total reflection-infra red (ATR-IR),13 C-, and29 Si-nuclear magnetic resonance (NMR) spectroscopic analyses of the ammonolysis product resulted in the detection of Si-NH-Si linkage and EtO group. The simultaneous thermogravimetric and mass spectrometry analyses of the EtOSZ under helium revealed cleavage of oxygen-carbon bond of the EtO group to evolve ethylene as a main gaseous species formed in-situ, which lead to the formation at 800 °C of quaternary amorphous Si-C-N with an extremely low carbon content (1...
December 5, 2017: Materials
Ryan S Doster, Lisa M Rogers, Jennifer A Gaddy, David M Aronoff
Tissue macrophages are derived from either circulating blood monocytes that originate in the bone marrow, or embryonic precursors that establish residence in tissues and are maintained independent of bone marrow progenitors. Macrophages perform diverse functions including tissue repair, the maintenance of homeostasis, and immune regulation. Recent studies have demonstrated that macrophages produce extracellular traps (ETs). ETs are an immune response by which a cell undergoes "ETosis" to release net-like material, with strands composed of cellular DNA that is studded with histones and cellular proteins...
2018: Journal of Innate Immunity
Y C Rocha Arrieta, M Rojas, G Vasquez, J Lopez
The release of DNA into the extracellular milieu by neutrophil during a process called NETosis has been postulated as an additional source of autoantigens; a process believed to be important in the pathogenesis of some autoimmune disease, such as systemic lupus erythematosus (SLE). However, it is not established if the B and T cells undergo the release of DNA to the extracellular milleu, in response to different stimuli. In this study, it was observed that the treatment of B and T cells with PMA, ionomycin and the serum from patients with SLE induced the extracellular DNA presence in B and T cells...
October 2017: Scandinavian Journal of Immunology
Jana Pieper, Maria Locke, Gunda Ruzaike, Stefanie Voigt, Ulrich Methner, Angela Berndt
The release of extracellular traps (ETs) by granulocytes is a unique strategy to stop the dissemination of microbial pathogens. This study was undertaken to elucidate the potential of avian granulocytes (heterophils) to form ETs that can arrest and kill Salmonella organisms. After in vitro exposure of isolated heterophils and in vivo infection of day-old chicks with Salmonella enterica subsp. enterica serovars Infantis (SI) or Enteritidis (SE), the generation of ETs as well as the trapping and survivability of Salmonella organisms in the ET meshwork were determined by means of microscopy and spectrophotometry...
June 2017: Veterinary Immunology and Immunopathology
Shigeharu Ueki, Nobuo Ohta, Masahide Takeda, Yasunori Konno, Makoto Hirokawa
PURPOSE OF REVIEW: Eosinophilic otitis media (EOM) is a refractory disease characterized by the accumulation of eosinophils in middle ear effusion and mucosa. We summarize current knowledge regarding the clinical characteristics and management of EOM. Although eosinophil activation in inflamed foci is involved in the pathogenesis of EOM, little is known about the fate of the eosinophils and aftermath of their cell death. We discuss the possibility that eosinophils undergo non-apoptotic cell death that worsens tissue damage and increases effusion viscosity...
May 2017: Current Allergy and Asthma Reports
Malin K Lange, Felipe Penagos-Tabares, Tamara Muñoz-Caro, Ulrich Gärtner, Helena Mejer, Roland Schaper, Carlos Hermosilla, Anja Taubert
BACKGROUND: Phagocyte-derived extracellular traps (ETs) were recently demonstrated mainly in vertebrate hosts as an important effector mechanism against invading parasites. In the present study we aimed to characterize gastropod-derived invertebrate extracellular phagocyte trap (InEPT) formation in response to larval stages of important canine and feline metastrongyloid lungworms. Gastropod haemocytes were isolated from the slug species Arion lusitanicus and Limax maximus, and the snail Achatina fulica, and exposed to larval stages of Angiostrongylus vasorum, Aelurostrongylus abstrusus and Troglostrongylus brevior and investigated for gastropod-derived InEPT formation...
January 31, 2017: Parasites & Vectors
Muhua Cao, Tao Li, Zhangxiu He, Lixiu Wang, Xiaoyan Yang, Yan Kou, Lili Zou, Xue Dong, Valerie A Novakovic, Yayan Bi, Junjie Kou, Bo Yu, Shaohong Fang, Jinghua Wang, Jin Zhou, Jialan Shi
Despite routine treatment of unselected acute promyelocytic leukemia (APL) with all- trans -retinoic acid (ATRA), early death because of hemorrhage remains unacceptably common, and the mechanism underlying this complication remains elusive. We have recently demonstrated that APL cells undergo a novel cell death program, termed ETosis, which involves release of extracellular chromatin. However, the role of promyelocytic extracellular chromatin in APL-associated coagulation remains unclear. Our objectives were to identify the novel role of ATRA-promoted extracellular chromatin in inducing a hypercoagulable and hyperfibrinolytic state in APL and to evaluate its interaction with fibrin and endothelial cells (ECs)...
March 30, 2017: Blood
Gen Kano, Bruce S Bochner, Nives Zimmermann
RATIONALE: Siglec-8 is a surface receptor predominantly expressed on human eosinophils where its ligation induces reactive oxygen species (ROS) formation and cell death. Since Siglec-8 has intracellular tyrosine-based motifs, we hypothesized that Src family kinases (SFKs) are involved in ROS formation and cell death induced by Siglec-8 engagement. METHODS: Human peripheral blood eosinophils were purified and incubated with anti-Siglec-8 monoclonal antibodies (mAb, agonist), IL-5, and SFK pharmacological inhibitors...
February 2017: Immunobiology
Chiou-Feng Lin, Chia-Ling Chen, Shun-Yi Chien, Po-Chun Tseng, Yu-Chih Wang, Tsung-Ting Tsai
We previously demonstrated that IFN-γ induces an autophagy-regulated mimic extracellular trap cell death (ETosis) in A549 human lung cancer cells. Regarding reactive oxygen species (ROS) are involved in ETosis, this study investigated the role of oxidative stress. After IFN-γ stimulation, a necrosis-like cell death mimic ETosis occurred accompanied by the inhibition of cell growth, aberrant nuclear staining, and nucleosome release. ROS were generated in a time-dependent manner with an increase in NADPH oxidase component protein expression...
2016: PloS One
Yumiko Yamauchi, Shigeharu Ueki, Yasunori Konno, Wataru Ito, Masahide Takeda, Yuka Nakamura, Junko Nishikawa, Yuki Moritoki, Ayumi Omokawa, Tomoo Saga, Makoto Hirokawa
Hepatocyte growth factor (HGF), originally identified as a potent mitogen for mature hepatocytes, is now recognized as a humoral mediator in inflammatory and immune responses. Previous studies indicated that HGF negatively regulated allergic airway inflammation. In view of eosinophils playing a role in the pathogenesis of asthma, especially in airway remodeling as a rich source of pro-fibrogenic mediators, the effects of HGF on the different types of eosinophil secretory functions were examined in this study...
December 2016: Cytokine
D Pérez, M C Muñoz, J M Molina, T Muñoz-Caro, L M R Silva, A Taubert, C Hermosilla, A Ruiz
Extracellular trap (ET) formation has been demonstrated as novel effector mechanism against diverse pathogens in polymorphonuclear neutrophils (PMN), eosinophils, mast cells, macrophages and recently also in monocytes. In the current study, we show that E. ninakohlyakimovae triggers the deliverance of monocyte-derived ETs in vitro. Fluorescence illustrations as well as scanning electron microscopy (SEM) analyses showed that monocyte-derived ET formation was rapidly induced upon exposure to viable sporozoites, sporocysts and oocysts of E...
August 30, 2016: Veterinary Parasitology
Helene Möllerherm, Maren von Köckritz-Blickwede, Katja Branitzki-Heinemann
Mast cells (MCs) have been shown to release their nuclear DNA and subsequently form mast cell extracellular traps (MCETs) comparable to neutrophil extracellular traps, which are able to entrap and kill various microbes. The formation of extracellular traps is associated with the disruption of the nuclear membrane, which leads to mixing of nuclear compounds with granule components and causes the death of the cell, a process called ETosis. The question arises why do MCs release MCETs although they are very well known as multifunctional long-living sentinel cells? MCs are known to play a role during allergic reactions and certain parasitic infections...
2016: Frontiers in Immunology
Liliana M R Silva, Tamara Muñoz-Caro, Rafael A Burgos, Maria A Hidalgo, Anja Taubert, Carlos Hermosilla
Professional mononuclear phagocytes such as polymorphonuclear neutrophils (PMN), monocytes, and macrophages are considered as the first line of defence against invasive pathogens. The formation of extracellular traps (ETs) by activated mononuclear phagocytes is meanwhile well accepted as an effector mechanism of the early host innate immune response acting against microbial infections. Recent investigations showed evidence that ETosis is a widely spread effector mechanism in vertebrates and invertebrates being utilized to entrap and kill bacteria, fungi, viruses, and protozoan parasites...
2016: Mediators of Inflammation
Shigeharu Ueki, Takahiro Tokunaga, Shigeharu Fujieda, Kohei Honda, Makoto Hirokawa, Lisa A Spencer, Peter F Weller
The traditional paradigm of eosinophils as end-stage damaging cells has mainly relied on their release of cytotoxic proteins. Cytokine-induced cell survival and secretion of granular contents from tissue-dwelling eosinophil are thought to be important mechanisms for eosinophilic inflammatory disorders, although the occurrence of cytolysis and its products (i.e., free extracellular granules) has been observed in affected lesions. Recent evidence indicates that activated eosinophils can exhibit a non-apoptotic cell death pathway, namely extracellular trap cell death (ETosis) that mediates the eosinophil cytolytic degranulation...
July 2016: Current Allergy and Asthma Reports
R Ma, T Li, M Cao, Y Si, X Wu, L Zhao, Z Yao, Y Zhang, S Fang, R Deng, V A Novakovic, Y Bi, J Kou, B Yu, S Yang, J Wang, J Zhou, J Shi
Acute promyelocytic leukemia (APL) cells exhibit disrupted regulation of cell death and differentiation, and therefore the fate of these leukemic cells is unclear. Here, we provide the first evidence that a small percentage of APL cells undergo a novel cell death pathway by releasing extracellular DNA traps (ETs) in untreated patients. Both APL and NB4 cells stimulated with APL serum had nuclear budding of vesicles filled with chromatin that leaked to the extracellular space when nuclear and cell membranes ruptured...
June 30, 2016: Cell Death & Disease
Tamara Muñoz-Caro, Mario C Rubio R, Liliana M R Silva, Gerd Magdowski, Ulrich Gärtner, Tom N McNeilly, Anja Taubert, Carlos Hermosilla
BACKGROUND: Polymorphonuclear neutrophil (PMN) and eosinophil extracellular trap (ETs) formation has recently been described as an important host effector mechanism against invading pathogens. So far, scarce evidence on metazoan-triggered ET formation has been published. We here describe for the first time Haemonchus contortus-triggered ETs being released by bovine PMN and ovine eosinophils in response to ensheathed and exsheathed third stage larvae (L3). METHODS: The visualization of ETs was achieved by SEM analysis...
November 26, 2015: Parasites & Vectors
Chiou-Feng Lin, Shun-Yi Chien, Chia-Ling Chen, Chia-Yuan Hsieh, Po-Chun Tseng, Yu-Chih Wang
Treatment of interferon-γ (IFN-γ) causes cell growth inhibition and cytotoxicity in lung epithelial malignancies. Regarding the induction of autophagy related to IFN-γ signaling, this study investigated the link between autophagy and IFN-γ cytotoxicity. In A549 human lung cancer cells, IFN-γ treatment induced concurrent apoptotic and nonapoptotic events. Unexpectedly, the nonapoptotic cells present mimic extracellular trap cell death (ETosis), which was regulated by caspase-3 and by autophagy induction through immunity-related GTPase family M protein 1 and activating transcription factor 6...
February 2016: Journal of Interferon & Cytokine Research
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