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Extracellular Traps

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https://www.readbyqxmd.com/read/28938688/drag-reducing-polymers-decrease-hepatic-injury-and-metastases-after-liver-ischemia-reperfusion
#1
Samer Tohme, Marina V Kameneva, Hamza O Yazdani, Vikas Sud, Julie Goswami, Patricia Loughran, Hai Huang, Richard L Simmons, Allan Tsung
INTRODUCTION: Surgery, a crucial therapeutic modality in the treatment of solid tumors, can induce sterile inflammatory processes which can result in metastatic progression. Liver ischemia and reperfusion (I/R) injury, an inevitable consequence of hepatic resection of metastases, has been shown to foster hepatic capture of circulating cancer cells and accelerate metastatic growth. Efforts to reduce these negative consequences have not been thoroughly investigated. Drag reducing polymers (DRPs) are blood-soluble macromolecules that can, in nanomolar concentrations, increase tissue perfusion, decrease vascular resistance and decrease near-wall microvascular concentration of neutrophils and platelets thereby possibly reducing the inflammatory microenvironment...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28936426/comparison-of-diabetic-and-non-diabetic-human-leukocytic-responses-to-different-capsule-types-of-klebsiella-pneumoniae-responsible-for-causing-pyogenic-liver-abscess
#2
I Russel Lee, Ethel Sng, Kok-Onn Lee, James S Molton, Monica Chan, Shirin Kalimuddin, Ezlyn Izharuddin, David C Lye, Sophia Archuleta, Yunn-Hwen Gan
The major risk factor for Klebsiella liver abscess (KLA) is type 2 diabetes mellitus (DM), but the immunological mechanisms involved in the increased susceptibility are poorly defined. We investigated the responses of neutrophils and peripheral blood mononuclear cells (PBMCs) to hypervirulent Klebsiella pneumoniae (hvKP), the causative agent of KLA. DNA and myeloperoxidase levels were elevated in the plasma of KLA patients compared to uninfected individuals indicating neutrophil activation, but diabetic status had no effect on these neutrophil extracellular trap (NET) biomarkers in both subject groups...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28935869/deoxyribonuclease-1-reduces-pathogenic-effects-of-cigarette-smoke-exposure-in-the-lung
#3
Paul T King, Roleen Sharma, Kim M O'Sullivan, Judy Callaghan, Lovisa Dousha, Belinda Thomas, Saleela Ruwanpura, Steven Lim, Michael W Farmer, Barton R Jennings, Michaela Finsterbusch, Gavin Brooks, Stavros Selemidis, Gary P Anderson, Stephen R Holdsworth, Philip G Bardin
Our aim was to investigate if deoxyribonuclease (DNase) 1 is a potential therapeutic agent to reduce pathogenic effects of cigarette smoke exposure in the lung. Cigarette smoke causes protease imbalance with excess production of proteases, which is a key process in the pathogenesis of emphysema. The mechanisms responsible for this effect are not well-defined. Our studies demonstrate both in vitro and in vivo that cigarette smoke significantly increases the expression of neutrophil and macrophage extracellular traps with coexpression of the pathogenic proteases, neutrophil elastase and matrix metalloproteinases 9 and 12...
September 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28931754/activated-signature-of-antiphospholipid-syndrome-neutrophils-reveals-potential-therapeutic-target
#4
Jason S Knight, He Meng, Patrick Coit, Srilakshmi Yalavarthi, Gautam Sule, Alex A Gandhi, Robert C Grenn, Levi F Mazza, Ramadan A Ali, Paul Renauer, Jonathan D Wren, Paula L Bockenstedt, Hui Wang, Daniel T Eitzman, Amr H Sawalha
Antiphospholipid antibodies, present in one-third of lupus patients, increase the risk of thrombosis. We recently reported a key role for neutrophils - neutrophil extracellular traps (NETs), in particular - in the thrombotic events that define antiphospholipid syndrome (APS). To further elucidate the role of neutrophils in APS, we performed a comprehensive transcriptome analysis of neutrophils isolated from patients with primary APS. Moreover, APS-associated venous thrombosis was modeled by treating mice with IgG prepared from APS patients, followed by partial restriction of blood flow through the inferior vena cava...
September 21, 2017: JCI Insight
https://www.readbyqxmd.com/read/28929912/in%C3%A2-vivo-induction-of-neutrophil-extracellular-traps-by-mycobacterium-tuberculosis-in-a-guinea-pig-model
#5
Georgina Filio-Rodríguez, Iris Estrada-García, Patricia Arce-Paredes, María M Moreno-Altamirano, Sergio Islas-Trujillo, M Dolores Ponce-Regalado, Oscar Rojas-Espinosa
In 2004, a novel mechanism of cellular death, called 'NETosis', was described in neutrophils. This mechanism, different from necrosis and apoptosis, is characterized by the release of chromatin webs admixed with microbicidal granular proteins and peptides (NETs). NETs trap and kill a variety of microorganisms. Diverse microorganisms, including Mycobacterium tuberculosis, are NET inducers in vitro. The aim of this study was to examine whether M. tuberculosis can also induce NETs in vivo and if the NETs are bactericidal to the microorganism...
January 1, 2017: Innate Immunity
https://www.readbyqxmd.com/read/28922428/diminished-neutrophil-extracellular-trap-net-formation-is-a-novel-innate-immune-deficiency-induced-by-acute-ethanol-exposure-in-polymicrobial-sepsis-which-can-be-rescued-by-cxcl1
#6
Liliang Jin, Sanjay Batra, Samithamby Jeyaseelan
Polymicrobial sepsis is the result of an exaggerated host immune response to bacterial pathogens. Animal models and human studies demonstrate that acute alcohol intoxication is a key risk factor for sepsis-induced mortality. Multiple chemokines, such as CXCL1, CXCL2 and CXCL5 are critical for neutrophil recruitment and proper function of neutrophils. However, it is not quite clear the mechanisms by which acute alcohol suppresses immune responses and whether alcohol-induced immunosuppression can be rescued by chemokines...
September 18, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28919990/pharmacological-targeting-of-peptidylarginine-deiminase-4-prevents-cancer-associated-kidney-injury-in-mice
#7
Jessica Cedervall, Anca Dragomir, Falk Saupe, Yanyu Zhang, Johan Ärnlöv, Erik Larsson, Anna Dimberg, Anders Larsson, Anna-Karin Olsson
Renal insufficiency is a frequent cancer-associated problem affecting more than half of all cancer patients at the time of diagnosis. To minimize nephrotoxic effects the dosage of anticancer drugs are reduced in these patients, leading to sub-optimal treatment efficacy. Despite the severity of this cancer-associated pathology, the molecular mechanisms, as well as therapeutic options, are still largely lacking. We here show that formation of intravascular tumor-induced neutrophil extracellular traps (NETs) is a cause of kidney injury in tumor-bearing mice...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28916704/delayed-neutrophil-apoptosis-enhances-net-formation-in-cystic-fibrosis
#8
Robert D Gray, Gareth Hardisty, Kate H Regan, Maeve Smith, Calum T Robb, Rodger Duffin, Annie Mackellar, Jennifer M Felton, Lily Paemka, Brian N McCullagh, Christopher D Lucas, David A Dorward, Edward F McKone, Gordon Cooke, Seamas C Donnelly, Pradeep K Singh, David A Stoltz, Christopher Haslett, Paul B McCray, Moira K B Whyte, Adriano G Rossi, Donald J Davidson
BACKGROUND: Cystic fibrosis (CF) lung disease is defined by large numbers of neutrophils and associated damaging products in the airway. Delayed neutrophil apoptosis is described in CF although it is unclear whether this is a primary neutrophil defect or a response to chronic inflammation. Increased levels of neutrophil extracellular traps (NETs) have been measured in CF and we aimed to investigate the causal relationship between these phenomena and their potential to serve as a driver of inflammation...
September 15, 2017: Thorax
https://www.readbyqxmd.com/read/28915803/tartrate-resistant-acid-phosphatase-trap-acp5-promotes-metastasis-related-properties-via-tgf%C3%AE-2-t%C3%AE-r-and-cd44-in-mda-mb-231-breast-cancer-cells
#9
Anja Reithmeier, Elena Panizza, Michael Krumpel, Lukas M Orre, Rui M M Branca, Janne Lehtiö, Barbro Ek-Rylander, Göran Andersson
BACKGROUND: Tartrate-resistant acid phosphatase (TRAP/ACP5), a metalloenzyme that is characteristic for its expression in activated osteoclasts and in macrophages, has recently gained considerable focus as a driver of metastasis and was associated with clinically relevant parameters of cancer progression and cancer aggressiveness. METHODS: MDA-MB-231 breast cancer cells with different TRAP expression levels (overexpression and knockdown) were generated and characterized for protein expression and activity levels...
September 15, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28899799/neutrophil-extracellular-traps-nets-in-autoimmune-diseases-a-comprehensive-review
#10
REVIEW
Keum Hwa Lee, Andreas Kronbichler, David Duck-Young Park, YoungMin Park, Hanwool Moon, Hyungdo Kim, Jun Hyug Choi, YoungSeo Choi, Songjoo Shim, Il Suk Lyu, Byung Hwan Yun, Yeonseung Han, Donghee Lee, Sang Yoon Lee, Byung Hun Yoo, Kyung Hwan Lee, Tai Lim Kim, Heonki Kim, Joo Sung Shim, Wonseok Nam, Heesung So, SooYeon Choi, Sangmok Lee, Jae Il Shin
The structures named neutrophil extracellular traps (NETs) are fibrous networks which protrude from the membrane of activated neutrophils. NETs are found in a variety of conditions, such as infection, malignancy, atherosclerosis, and autoimmune diseases such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV), psoriasis, and gout. The impact of NETs on the development mechanisms of autoimmune diseases are proposed to arise from an imbalance between "NETosis" which is a process of NET formation and NET degradation...
September 9, 2017: Autoimmunity Reviews
https://www.readbyqxmd.com/read/28890882/neutrophils-to-the-roscue-mechanisms-of-nadph-oxidase-activation-and-bacterial-resistance
#11
REVIEW
Giang T Nguyen, Erin R Green, Joan Mecsas
Reactive oxygen species (ROS) generated by NADPH oxidase play an important role in antimicrobial host defense and inflammation. Their deficiency in humans results in recurrent and severe bacterial infections, while their unregulated release leads to pathology from excessive inflammation. The release of high concentrations of ROS aids in clearance of invading bacteria. Localization of ROS release to phagosomes containing pathogens limits tissue damage. Host immune cells, like neutrophils, also known as PMNs, will release large amounts of ROS at the site of infection following the activation of surface receptors...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28890131/characterization-of-systemic-neutrophil-function-in-patients-undergoing-colorectal-cancer-resection
#12
Jonathan J R Richardson, Charles Hendrickse, Fang Gao-Smith, David R Thickett
BACKGROUND: In patients with colorectal cancer, the generation and maintenance of a systemic inflammatory response is associated with poor outcomes. Neutrophils have been implicated in the prognosis of such patients, but little is known about their functional response to surgery. This study was conducted to characterize neutrophil function of patients undergoing colorectal cancer resection. MATERIALS AND METHODS: Systemic neutrophils were isolated from patients with colorectal cancer who underwent surgical resection preoperatively (day 0) and postoperatively (day 1 and day 3)...
September 7, 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28889199/oral-delivery-of-staphylococcal-nuclease-by-lactococcus-lactis-prevents-type-1-diabetes-mellitus-in-nod-mice
#13
Junchao Lang, Xiaoke Wang, Kunfeng Liu, Dongmei He, Pancong Niu, Rongyue Cao, Liang Jin, Jie Wu
Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by the self-destruction of insulin-producing β cells. Recently, studies have revealed that neutrophils contribute to the early pathological injury to the pancreas, predominantly via the formation of neutrophil extracellular traps (NETs). To determine whether early intervention targeting NETs with staphylococcal nuclease (SNase) can delay the onset of T1DM, non-obese diabetic (NOD) mice were orally administered recombinant Lactococcus lactis (L...
September 9, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28884828/neutrophil-extracellular-traps-in-acrolein-promoted-hepatic-ischemia-reperfusion-injury-therapeutic-potential-of-nox2-and-p38mapk-inhibitors
#14
Arumugam Suyavaran, Kesthuru Subbiah Girish, K Kemparaju, Chinnasamy Thirunavukkarasu
Neutrophil is a significant contributor to ischemia reperfusion (IR) induced liver tissue damage. However, the underlying mechanisms of IR induced innate immune activation and liver damage is not quite clear. Our study sheds light on the role of chronic oxidative stress end products in worsening the IR inflammatory process by neutrophil recruitment and activation following liver surgery. We employed specific inhibitors for molecular targets - NOX2 (NADPH oxidase 2) and P38 MAPK (Mitogen activated protein kinase) signal to counteract neutrophil activation and neutrophil extracellular trap (NET) release induced liver damage in IR injury...
September 8, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28881492/a-novel-elane-mutation-associated-with-inflammatory-arthritis-defective-netosis-and-recurrent-parvoviral-infection
#15
Uma Thanarajasingam, Mark A Jensen, Jessica M Dorschner, Theresa Wampler Muskardin, Yogita Ghodke-Puranik, Monica Purmalek, Elias Eliopoulos, Maria I Zervou, George N Goulielmos, Matthew Howard, Mariana J Kaplan, Timothy B Niewold
OBJECTIVE: We describe a 38-year-old woman presenting with a history of inflammatory arthritis, rash and daily fevers. She was noted to have chronic parvoviral infection with persistently detectable viral titers and a novel mutation in the ELANE gene. ELANE encodes neutrophil elastase, a neutrophil serine protease with important antimicrobial effects and is found as part of neutrophil extracellular trap (NET) complexes. Pathogenic ELANE mutations have been described in forms of hereditary neutropenia...
September 7, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28880680/the-effect-and-possible-clinical-efficacy-of-in-vivo-inhibition-of-neutrophil-extracellular-traps-by-blockade-of-pi3k-gamma-on-the-pathogenesis-of-microscopic-polyangiitis
#16
Hirotaka Kimura, Yasushi Matsuyama, Sachiko Araki, Atsushi Koizumi, Yumi Kariya, Shunsuke Takasuga, Satoshi Eguchi, Hiroki Nakanishi, Junko Sasaki, Takehiko Sasaki
OBJECTIVE: Neutrophil extracellular traps (NETs) are peculiar structures composed of the externalized chromatin with intracellular proteins and formed by activated neutrophils in a reactive oxygen species (ROS)-dependent manner. Aberrant NETs are considered to be autoantigens for anti-neutrophil cytoplasmic antibodies (ANCAs) underling the development of microscopic polyangiitis (MPA). However, little is known regarding the therapeutic efficacy of in vivo inhibition of NET formation (NETosis) on MPA pathogenesis...
September 7, 2017: Modern Rheumatology
https://www.readbyqxmd.com/read/28878626/map-kinase-phosphatase-3-mkp3-preserves-norepinephrine-transporter-activity-by-modulating-erk1-2-kinase-mediated-gene-expression
#17
Ole V Mortensen, Mads B Larsen, Susan G Amara
The norepinephrine transporter (NET) mediates the clearance of norepinephrine (NE) from the extracellular space and is a target of therapeutic antidepressants and psychostimulants. Previously we identified a MAP kinase phosphatase 3 (MKP3), as an important modulator of protein kinase C (PKC) mediated internalization of the related dopamine transporter (DAT). Here we show that MKP3 decreases PKC-mediated down regulation of NET expressed in PC12 cells. We demonstrate that this process involves a PKC-stimulated decrease of NET surface expression that is dependent on dynamin...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28875161/crystal-structures-of-a-zip-zinc-transporter-reveal-a-binuclear-metal-center-in-the-transport-pathway
#18
Tuo Zhang, Jian Liu, Matthias Fellner, Chi Zhang, Dexin Sui, Jian Hu
Zrt/Irt-like proteins (ZIPs) play fundamental roles in metal metabolism/homeostasis and are broadly involved in numerous physiological and pathological processes. The lack of high-resolution structure of the ZIPs hinders understanding of the metal transport mechanism. We report two crystal structures of a prokaryotic ZIP in lipidic cubic phase with bound metal substrates (Cd(2+) at 2.7 Å and Zn(2+) at 2.4 Å). The structures revealed a novel 3+2+3TM architecture and an inward-open conformation occluded at the extracellular side...
August 2017: Science Advances
https://www.readbyqxmd.com/read/28874114/dual-transcriptome-of-the-immediate-neutrophil-and-candida-albicans-interplay
#19
Maria J Niemiec, Christian Grumaz, David Ermert, Christiane Desel, Madhu Shankar, José Pedro Lopes, Ian G Mills, Philip Stevens, Kai Sohn, Constantin F Urban
BACKGROUND: Neutrophils are traditionally considered transcriptionally inactive. Compared to other immune cells, little is known about their transcriptional profile during interaction with pathogens. METHODS: We analyzed the meta-transcriptome of the neutrophil-Candida albicans interplay and the transcriptome of C. albicans challenged with neutrophil extracellular traps (NETs) by RNA-Seq, considering yeast and hypha individually in each approach. RESULTS: The neutrophil response to C...
September 6, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28870032/-neutrophil-extracellular-traps-induced-endothelial-cell-damage-in-the-pathogenesis-of-dermatomyositis-associated-interstitial-lung-disease
#20
Y Zhang, B Yan, Y Liu
Objective: To explore the role of neutrophil extracellular traps (NETs)-induced endothelial cell damage in the pathogenesis of dermatomyositis (DM)-associated interstitial lung disease(ILD). Methods: Serum free DNA and krebs von den lungen-6 (KL-6) level were tested in healthy controls, dermatomyositis patients with or without interstitial lung disease (DM-ILD and DM-NILD). Subjects' peripheral blood neutrophils were stimulated with phorbol 12-myristate 13-acetate (PMA), then human umbilical vein endothelial cells (HUVECs) were co-cultured with NETs...
September 1, 2017: Zhonghua Nei Ke za Zhi [Chinese Journal of Internal Medicine]
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