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https://www.readbyqxmd.com/read/28634421/the-role-of-von-willebrand-factor-in-vascular-inflammation-from-pathogenesis-to-targeted-therapy
#1
REVIEW
Felice Gragnano, Simona Sperlongano, Enrica Golia, Francesco Natale, Renatomaria Bianchi, Mario Crisci, Fabio Fimiani, Ivana Pariggiano, Vincenzo Diana, Andreina Carbone, Arturo Cesaro, Claudia Concilio, Giuseppe Limongelli, Mariagiovanna Russo, Paolo Calabrò
Beyond its role in hemostasis, von Willebrand factor (VWF) is an emerging mediator of vascular inflammation. Recent studies highlight the involvement of VWF and its regulator, ADAMTS13, in mechanisms that underlie vascular inflammation and immunothrombosis, like leukocyte rolling, adhesion, and extravasation; vascular permeability; ischemia/reperfusion injury; complements activation; and NETosis. The VWF/ADAMTS13 axis is implicated in the pathogenesis of atherosclerosis, promoting plaque formation and inflammation through macrophage and neutrophil recruitment in inflamed lesions...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28611772/bovine-polymorphonuclear-neutrophils-cast-neutrophil-extracellular-traps-against-the-abortive-parasite-neospora-caninum
#2
Rodolfo Villagra-Blanco, Liliana M R Silva, Tamara Muñoz-Caro, Zhengtao Yang, Jianhua Li, Ulrich Gärtner, Anja Taubert, Xichen Zhang, Carlos Hermosilla
Neospora caninum represents a relevant apicomplexan parasite causing severe reproductive disorders in cattle worldwide. Neutrophil extracellular trap (NET) generation was recently described as an efficient defense mechanism of polymorphonuclear neutrophils (PMN) acting against different parasites. In vitro interactions of bovine PMN with N. caninum were analyzed at different ratios and time spans. Extracellular DNA staining was used to illustrate the typical molecules of NETs [i.e., histones (H3), neutrophil elastase (NE), myeloperoxidase (MPO), pentraxin] via antibody-based immunofluorescence analyses...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28611461/jnk-activation-turns-on-lps-and-gram-negative-bacteria-induced-nadph-oxidase-dependent-suicidal-netosis
#3
Meraj A Khan, Armin Farahvash, David N Douda, Johann-Christoph Licht, Hartmut Grasemann, Neil Sweezey, Nades Palaniyar
Neutrophils cast neutrophil extracellular traps (NETs) to ensnare microbial pathogens. Nevertheless, the molecular rheostats that regulate NETosis in response to bacteria are not clearly established. We hypothesized that stress-activated protein kinase or c-Jun N-terminal Kinase (SAPK/JNK) is a molecular switch that turns on NETosis in response to increasing concentrations of lipopolysaccharide (LPS)- and Gram-negative bacteria. Here we show that Escherichia coli LPS (0111:B4; 10-25 μg/ml), but not phorbol myristate acetate (PMA), activates JNK in human neutrophils in a dose-dependent manner...
June 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28606989/tlr7-8-activation-in-neutrophils-impairs-immune-complex-phagocytosis-through-shedding-of-fcgriia
#4
Christian Lood, Sabine Arve, Jeffrey Ledbetter, Keith B Elkon
Neutrophils play a crucial role in host defense. However, neutrophil activation is also linked to autoimmune diseases such as systemic lupus erythematosus (SLE), where nucleic acid-containing immune complexes (IC) drive inflammation. The role of Toll-like receptor (TLR) signaling in processing of SLE ICs and downstream inflammatory neutrophil effector functions is not known. We observed that TLR7/8 activation leads to a furin-dependent proteolytic cleavage of the N-terminal part of FcgRIIA, shifting neutrophils away from phagocytosis of ICs toward the programmed form of necrosis, NETosis...
June 12, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28606032/metformin-a-new-era-for-an-old-drug-in-the-treatment-of-immune-mediated-disease
#5
Mark Schuiveling, Nadia Vazirpanah, Timothy R D J Radstake, Maili Zimmermann, Jasper C A Broen
Metformin, a widely prescribed blood glucose normalizing antidiabetic drug, is now beginning to receive increasing attention due to its potential anti-inflammatory properties. Metformin suppresses immune responses mainly through its direct effect on the cellular functions of various immune cell types by induction of AMPK and subsequent inhibition of mTORC1, and by inhibition of mitochondrial ROS production. Among key immune events, this results in inhibited monocyte to macrophage differentiation and restrained inflammatory capacity of activated macrophages...
June 12, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28589151/advanced-role-of-neutrophils-in-common-respiratory-diseases
#6
REVIEW
Jinping Liu, Zhiqiang Pang, Guoqiang Wang, Xuewa Guan, Keyong Fang, Ziyan Wang, Fang Wang
Respiratory diseases, always being a threat towards the health of people all over the world, are most tightly associated with immune system. Neutrophils serve as an important component of immune defense barrier linking innate and adaptive immunity. They participate in the clearance of exogenous pathogens and endogenous cell debris and play an essential role in the pathogenesis of many respiratory diseases. However, the pathological mechanism of neutrophils remains complex and obscure. The traditional roles of neutrophils in severe asthma, chronic obstructive pulmonary diseases (COPD), pneumonia, lung cancer, pulmonary fibrosis, bronchitis, and bronchiolitis had already been reviewed...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28583201/molecular-signatures-of-neutrophil-extracellular-traps-in-human-visceral-leishmaniasis
#7
Luiz Gustavo Gardinassi, Thiago S DeSouza-Vieira, Naila O da Silva, Gustavo R Garcia, Valéria M Borges, Roseane N S Campos, Roque P de Almeida, Isabel K F de Miranda Santos, Elvira M Saraiva
BACKGROUND: Infections with parasites of the Leishmania donovani complex result in clinical outcomes that range from asymptomatic infection to severe and fatal visceral leishmaniasis (VL). Neutrophils are major players of the immune response against Leishmania, but their contribution to distinct states of infection is unknown. Gene expression data suggest the activation of the NETosis pathway during human visceral leishmaniasis. Thus, we conducted an exploratory study to evaluate NET-related molecules in retrospective sera from VL patients, asymptomatic individuals and uninfected endemic controls...
June 6, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28574339/diverse-stimuli-engage-different-neutrophil-extracellular-trap-pathways
#8
Elaine F Kenny, Alf Herzig, Renate Krüger, Aaron Muth, Santanu Mondal, Paul R Thompson, Volker Brinkmann, Horst Von Bernuth, Arturo Zychlinsky
Neutrophils release neutrophil extracellular traps (NETs) which ensnare pathogens and have pathogenic functions in diverse diseases. We examined the NETosis pathways induced by five stimuli; PMA, the calcium ionophore A23187, nigericin, Candida albicans and Group B Streptococcus. We studied NET production in neutrophils from healthy donors with inhibitors of molecules crucial to PMA induced NETs including protein kinase C, calcium, reactive oxygen species, the enzymes myeloperoxidase (MPO) and neutrophil elastase...
June 2, 2017: ELife
https://www.readbyqxmd.com/read/28536276/persistent-immune-stimulation-exacerbates-genetically-driven-myeloproliferative-disorders-via-stromal-remodeling
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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...
June 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
#16
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
#17
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 multifunctional 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...
May 26, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28382034/neutrophil-extracellular-traps-of-cynoglossus-semilaevis-production-characteristics-and-antibacterial-effect
#18
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
#19
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
#20
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
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