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Neutrophil extracellular trap

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https://www.readbyqxmd.com/read/28544690/deficiency-of-complement-1r-subcomponent-in-early-onset-sle-role-for-disease-modifying-alleles-in-a-monogenic-disease
#1
Erkan Demirkaya, Qing Zhou, Carolyne K Smith, Michael J Ombrello, Natalie Deuitch, Wanxia L Tsai, Patrycja Hoffmann, Elaine F Remmers, Masaki Takeuchi, Yong Hwan Park, JaeJin Chae, Kenan Barut, Dogan Simsek, Amra Adrovic, Sezgin Sahin, Salim Caliskan, Settara C Chandrasekharappa, Sarfaraz A Hasni, Amanda K Ombrello, Massimo Gadina, Daniel L Kastner, Mariana J Kaplan, Ozgur Kasapcopur, Ivona Aksentijevich
OBJECTIVE: To identify a genetic cause of early-onset systemic lupus erythematosus (SLE) in a large consanguineous family from Turkey and to study the mechanisms of disease. METHODS: We performed whole exome sequencing (WES) and SNP array genotyping in affected and unaffected family members. Protein studies, gene expression, cytokine profiling, neutrophil extracellular trap formation, and presence of low-density granulocytes were evaluated in patient primary cells and serum samples...
May 23, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28542869/tanshinone-iia-ameliorates-chronic-arthritis-in-mice-by-modulating-neutrophil-activities
#2
Shan Zhang, Guangrui Huang, Kai Yuan, Qingqing Zhu, Honghao Sheng, Ruipeng Yu, Guangbin Luo, Anlong Xu
AIMS: Rheumatoid arthritis (RA) is a chronic immune inflammatory disease mediated by the influx of immune cells into the synovial joint space. As Tanshinone IIA (TIIA) has potent antioxidant and anti-inflammatory activities, we used the adjuvant-induced arthritis (AA) murine model of RA to investigate the impact of TIIA on RA and immune cell activation. METHODS: The anti-arthritic activity of TIIA was investigated in an adjuvant-induced arthritis model of RA in mice...
May 24, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28542146/the-role-of-extracellular-histone-in-organ-injury
#3
REVIEW
Eleanor Silk, Hailin Zhao, Hao Weng, Daqing Ma
Histones are intra-nuclear cationic proteins that are present in all eukaryotic cells and are highly conserved across species. Within the nucleus, they provide structural stability to chromatin and regulate gene expression. Histone may be released into the extracellular space in three forms: freely, as a DNA-bound nucleosome or as part of neutrophil extracellular traps, and all three can be detected in serum after significant cellular death such as sepsis, trauma, ischaemia/reperfusion injury and autoimmune disease...
May 25, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28536276/persistent-immune-stimulation-exacerbates-genetically-driven-myeloproliferative-disorders-via-stromal-remodeling
#4
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/28526137/cellular-and-molecular-mechanisms-of-autoimmunity-and-lupus-nephritis
#5
S K Devarapu, G Lorenz, O P Kulkarni, H-J Anders, S R Mulay
Autoimmunity involves immune responses directed against self, which are a result of defective self/foreign distinction of the immune system, leading to proliferation of self-reactive lymphocytes, and is characterized by systemic, as well as tissue-specific, inflammation. Numerous mechanisms operate to ensure the immune tolerance to self-antigens. However, monogenetic defects or genetic variants that weaken immune tolerance render susceptibility to the loss of immune tolerance, which is further triggered by environmental factors...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28524191/thermal-scribing-to-prototype-plastic-microfluidic-devices-applied-to-study-the-formation-of-neutrophil-extracellular-traps
#6
Arvind Chandrasekaran, Nikita Kalashnikov, Roni Rayes, Claire Wang, Jonathan Spicer, Christopher Moraes
Innovation in microfluidics-based biological research has been aided by the growing accessibility of versatile microscale fabrication techniques, particularly in rapid prototyping of elastomeric polydimethylsiloxane (PDMS) based devices. However, the use of PDMS presents considerable and often unexpected limitations, particularly in interpreting and validating biological data. To rapidly prototype microfluidic culture systems in conventional plastics commonly used in cell culture, we developed 'thermal scribing', a one-step micromachining technique in which thermoplastics are locally patterned by a heated tip, moving in user-controlled patterns...
May 19, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/28523279/increased-neutrophil-extracellular-trap-formation-in-uremia-is-associated-with-chronic-inflammation-and-prevalent-coronary-artery-disease
#7
Jwa-Kyung Kim, Chang-Won Hong, Mi Jin Park, Young Rim Song, Hyung Jik Kim, Sung Gyun Kim
Background. Neutrophils are involved in the pathogenesis of atherosclerosis by neutrophil extracellular trap (NET) formation. We hypothesized that the NET formation of neutrophils might be changed in end-stage renal disease (ESRD) patients, explaining their higher incidence of coronary artery diseases (CAD). Method. A cross-sectional study was performed in 60 maintenance hemodialysis (MHD) patients, 30 age- and sex-matched healthy individuals (HV, negative control), and 30 patients with acute infection (positive control)...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28515366/experimental-lupus-is-aggravated-in-mouse-strains-with-impaired-induction-of-neutrophil-extracellular-traps
#8
Deborah Kienhöfer, Jonas Hahn, Julia Stoof, Janka Zsófia Csepregi, Christiane Reinwald, Vilma Urbonaviciute, Caroline Johnsson, Christian Maueröder, Malgorzata J Podolska, Mona H Biermann, Moritz Leppkes, Thomas Harrer, Malin Hultqvist, Peter Olofsson, Luis E Munoz, Attila Mocsai, Martin Herrmann, Georg Schett, Rikard Holmdahl, Markus H Hoffmann
Many effector mechanisms of neutrophils have been implicated in the pathogenesis of systemic lupus erythematosus (SLE). Neutrophil extracellular traps (NETs) have been assigned a particularly detrimental role. Here we investigated the functional impact of neutrophils and NETs on a mouse model of lupus triggered by intraperitoneal injection of the cell death-inducing alkane pristane. Pristane-induced lupus (PIL) was aggravated in 2 mouse strains with impaired induction of NET formation, i.e., NOX2-deficient (Ncf1-mutated) and peptidyl arginine deiminase 4-deficient (PAD4-deficient) mice, as seen from elevated levels of antinuclear autoantibodies (ANAs) and exacerbated glomerulonephritis...
May 18, 2017: JCI Insight
https://www.readbyqxmd.com/read/28515361/lupus-and-proliferative-nephritis-are-pad4-independent-in-murine-models
#9
Rachael A Gordon, Jan M Herter, Florencia Rosetti, Allison M Campbell, Hiroshi Nishi, Michael Kashgarian, Sheldon I Bastacky, Anthony Marinov, Kevin M Nickerson, Tanya N Mayadas, Mark J Shlomchik
Though recent reports suggest that neutrophil extracellular traps (NETs) are a source of antigenic nucleic acids in systemic lupus erythematosus (SLE), we recently showed that inhibition of NETs by targeting the NADPH oxidase complex via cytochrome b-245, β polypeptide (cybb) deletion exacerbated disease in the MRL.Faslpr lupus mouse model. While these data challenge the paradigm that NETs promote lupus, it is conceivable that global regulatory properties of cybb and cybb-independent NETs confound these findings...
May 18, 2017: JCI Insight
https://www.readbyqxmd.com/read/28515093/circulating-soluble-p-selectin-must-dimerize-to-promote-inflammation-and-coagulation-in-mice
#10
Sumith R Panicker, Padmaja Mehta-D'souza, Nan Zhang, Arkadiusz G Klopocki, Bojing Shao, Rodger P McEver
Leukocyte adhesion to P-selectin on activated platelets and endothelial cells induces shedding of the P-selectin ectodomain into the circulation. Plasma soluble P-selectin (sP-selectin) is elevated 3-4-fold in patients with cardiovascular disease. Circulating sP-selectin is thought to trigger signaling in leukocytes that directly contributes to inflammation and thrombosis. However, sP-selectin likely circulates as a monomer, and in vitro studies suggest that sP-selectin must dimerize to induce signaling in leukocytes...
May 17, 2017: Blood
https://www.readbyqxmd.com/read/28515091/angiotensin-converting-enzyme-enhances-the-oxidative-response-and-bactericidal-activity-of-neutrophils
#11
Zakir Khan, Xiao Z Shen, Ellen A Bernstein, Jorge F Giani, Masahiro Eriguchi, Tuantuan V Zhao, Romer A Gonzalez-Villalobos, Sebastien Fuchs, George Y Liu, Kenneth E Bernstein
Angiotensin converting enzyme (ACE) inhibitors are widely used to reduce blood pressure. Here, we examined if ACE is important for the antibacterial effectiveness of neutrophils. ACE knockout mice or mice treated with an ACE inhibitor were more susceptible to bacterial infection by methicillin-resistant S. aureus (MRSA). In contrast, mice over expressing ACE in neutrophils (Neu(ACE) mice) have increased resistance to MRSA, and better in vitro killing of MRSA, P. aeruginosa, and K. pneumoniae ACE overexpression increased neutrophil production of reactive oxygen species (ROS) following MRSA challenge, an effect independent of the angiotensin II AT1 receptor...
May 17, 2017: Blood
https://www.readbyqxmd.com/read/28506850/neutrophil-extracellular-traps-are-associated-with-disease-severity-and-microbiota-diversity-in-chronic-obstructive-pulmonary-disease
#12
Alison J Dicker, Megan L Crichton, Eleanor G Pumphrey, Andrew J Cassidy, Guillermo Suarez-Cuartin, Oriol Sibila, Elizabeth Furrie, Christopher J Fong, Wasyla Ibrahim, Gill Brady, Gisli G Einarsson, J Stuart Elborn, Stuart Schembri, Sara E Marshall, Colin Na Palmer, James D Chalmers
BACKGROUND: Neutrophil extracellular traps (NETs) have been observed in the airway in COPD, but their clinical and pathophysiological implications have not been defined. OBJECTIVE: To determine if NETs are associated with disease severity in COPD, and how they are associated with microbiota composition and airway neutrophil function. METHODS: NET protein complexes (DNA-Elastase and Histone-Elastase complexes), cell free DNA and neutrophil biomarkers were quantified in soluble sputum and serum from COPD patients during periods of disease stability and during exacerbations, and compared to clinical measures of disease severity and sputum microbiome...
May 12, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28495931/neutrophil-extracellular-traps-drive-endothelial-to-mesenchymal-transition
#13
Elmar Pieterse, Nils Rother, Marjolein Garsen, Julia Hofstra, Simon Satchell, Markus Hoffmann, Markus Loeven, Hanneke Knaapen, Olivier van der Heijden, Jo Berden, Luuk Hilbrands, Johan van der Vlag
OBJECTIVE: An excessive release and impaired degradation of neutrophil extracellular traps (NETs) leads to the continuous exposure of NETs to the endothelium in a variety of hematologic and autoimmune disorders, including lupus nephritis. This study aims to unravel the mechanisms through which NETs jeopardize vascular integrity. APPROACH AND RESULTS: Microvascular and macrovascular endothelial cells were exposed to NETs, and subsequent effects on endothelial integrity and function were determined in vitro and in vivo...
May 11, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28495856/flavored-e-cigarette-liquids-and-cinnamaldehyde-impair-respiratory-innate-immune-cell-function
#14
Phillip Wayne Clapp, Erica Ann Pawlak, Justin Trevor Lackey, James Edward Keating, Steven L Reeber, Gary L Glish, Ilona Jaspers
Innate immune cells of the respiratory tract are the first line of defense against pathogenic and environmental insults. Failure of these cells to perform their immune functions leaves the host susceptible to infection, and may contribute to impaired resolution of inflammation. While combustible tobacco cigarettes have been shown to suppress respiratory immune cell function, the effects of flavored electronic cigarette liquids (e-liquids) and individual flavoring agents on respiratory immune cell responses are unknown...
May 11, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28487062/mitochondrial-damps-are-released-during-cardiopulmonary-bypass-surgery-and-are-associated-with-postoperative-atrial-fibrillation
#15
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
#16
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/28471497/haploinsufficiency-of-nadph-oxidase-subunit-ncf2-is-sufficient-to-accelerate-full-blown-lupus-in-nzm-2328-mice
#17
Chaim O Jacob, Ning Yu, Dae-Goon Yoo, Lizet J Perez-Zapata, Emilia Alina Barbu, Mariana J Kaplan, Monica Purmalek, Jeanette T Pingel, Rachel A Idol, Mary C Dinauer
OBJECTIVE: We have previously established that NCF2 (Neutrophil cytosolic factor 2) is a lupus predisposing gene and identified lupus patients with point mutations that are predicted to cause reduced NADPH oxidase activity. This study was undertaken to investigate the relationship between reduced leukocyte NADPH oxidase activity and immune dysregulation associated with SLE. METHODS: We generated NCF2-null mice, in which NADPH oxidase activity is absent, on the non-autoimmune C57BL/6 background and on the NZM...
May 4, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28468761/cd177-neutrophils-as-functionally-activated-neutrophils-negatively-regulate-ibd
#18
Guangxi Zhou, Lin Yu, Leilei Fang, Wenjing Yang, Tianming Yu, Yinglei Miao, Minhu Chen, Kaichun Wu, Feidi Chen, Yingzi Cong, Zhanju Liu
BACKGROUND: Neutrophils are accumulated in inflamed mucosa of IBD and play an important role in the pathogenesis. CD177 is expressed in neutrophils specifically and upregulated during inflammation. However, the role of CD177(+) neutrophils in pathogenesis of IBD remains elusive. MATERIALS AND METHODS: Expression of CD177 was analysed in peripheral blood and intestinal mucosa from patients with IBD using quantitative RT-PCR, flow cytometry and immunohistochemistry...
May 3, 2017: Gut
https://www.readbyqxmd.com/read/28467984/neutrophil-extracellular-traps-stimulate-proinflammatory-responses-in-human-airway-epithelial-cells
#19
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
#20
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
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