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Extracellular DNA NET-Works With Dire Consequences for Health.

Published on Aug 2, 2019in Circulation Research15.862
· DOI :10.1161/CIRCRESAHA.119.314581
Nicoletta Sorvillo10
Estimated H-index: 10
(Harvard University),
Deya Cherpokova10
Estimated H-index: 10
(Harvard University)
+ 1 AuthorsDenisa D. Wagner105
Estimated H-index: 105
(Harvard University)
Sources
Abstract
Neutrophils play a central role in innate immune defense. Advances in neutrophil biology have brought to light the capacity of neutrophils to release their decondensed chromatin and form large extr...
  • References (216)
  • Citations (5)
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References216
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#1Fernanda Vargas e Silva Castanheira (U of C: University of Calgary)H-Index: 2
#2Paul Kubes (U of C: University of Calgary)H-Index: 94
Neutrophils are an absolutely essential part of the innate immune system, playing an essential role in the control of infectious diseases but more recently are also being viewed as important players in tissue repair. Neutrophils are able to counteract an infection through phagocytosis and/or the release of neutrophil extracellular traps (NETs). By contrast, neutrophils help repair damaged tissues, limiting NET production but still phagocytosing debris. However, when inflammation is recurrent, or...
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#2Quinte BrasterH-Index: 4
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The perpetuation of inflammation is an important pathophysiological contributor to the global medical burden. Chronic inflammation is promoted by non-programmed cell death1,2; however, how inflammation is instigated, its cellular and molecular mediators, and its therapeutic value are poorly defined. Here we use mouse models of atherosclerosis—a major underlying cause of mortality worldwide—to demonstrate that extracellular histone H4-mediated membrane lysis of smooth muscle cells (SMCs) triggers...
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#1Marrah E. Lachowicz-Scroggins (UCSF: University of California, San Francisco)H-Index: 9
#2Eleanor M. Dunican (UCD: University College Dublin)H-Index: 10
Last. John V. Fahy (UCSF: University of California, San Francisco)H-Index: 73
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Rationale: Extracellular DNA (eDNA) and neutrophil extracellular traps (NETs) are implicated in multiple inflammatory diseases. NETs mediate inflammasome activation and IL-1β secretion from monocyt...
6 CitationsSource
#1Ramadan A. Ali (UM: University of Michigan)H-Index: 3
#2Alex A. Gandhi (UM: University of Michigan)H-Index: 3
Last. Jason S. Knight (UM: University of Michigan)H-Index: 27
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Potentiation of neutrophil extracellular trap (NET) release is one mechanism by which antiphospholipid antibodies (aPL Abs) effect thrombotic events in patients with antiphospholipid syndrome (APS). Surface adenosine receptors trigger cyclic AMP (cAMP) formation in neutrophils, and this mechanism has been proposed to regulate NETosis in some contexts. Here we report that selective agonism of the adenosine A2A receptor (CGS21680) suppresses aPL Ab-mediated NETosis in protein kinase A-dependent fa...
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#1Ajitha Thanabalasuriar (AstraZeneca)H-Index: 2
#2Brittney N.V. Scott (U of C: University of Calgary)H-Index: 4
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Summary Bacterial biofilm infections are difficult to eradicate because of antibiotic insusceptibility and high recurrence rates. Biofilm formation by Pseudomonas aeruginosa, a leading cause of bacterial keratitis, is facilitated by the bacterial Psl exopolysaccharide and associated with heightened virulence. Using intravital microscopy, we observed that neutrophilic recruitment to corneal infections limits P. aeruginosa biofilms to the outer eye surface, preventing bacterial dissemination. Neut...
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#1Alan R. Tall (Columbia University)H-Index: 114
#2Marit Westerterp (UMCG: University Medical Center Groningen)H-Index: 26
Activation of macrophage inflammasomes leads to interleukin (IL)-1b and IL-18 secretion and promotes atherosclerosis and its complications in mice and humans. However, the specific role and underlying mechanisms of the inflammasome in atherogenesis are topics of active research. Several studies in hyperlipidemic mouse models found that the NLRP3 inflammasome contributes to atherosclerosis, but recent work suggests that a second hit, such as defective cholesterol efflux or accumulation of oxidize...
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#1Jose Perdomo (UNSW: University of New South Wales)H-Index: 12
#2Halina H. L. Leung (UNSW: University of New South Wales)H-Index: 4
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Heparin-induced thrombocytopenia/thrombosis (HIT) is a serious immune reaction to heparins, characterized by thrombocytopenia and often severe thrombosis with high morbidity and mortality. HIT is mediated by IgG antibodies against heparin/platelet factor 4 antigenic complexes. These complexes are thought to activate platelets leading to thrombocytopenia and thrombosis. Here we show that HIT immune complexes induce NETosis via interaction with FcγRIIa on neutrophils and through neutrophil-platele...
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IntroductionThe ultrastructure and cellular composition of thrombi has a profound effect on the outcome of acute ischemic stroke (AIS), coronary (CAD) and peripheral artery disease (PAD). Activated neutrophils release a web-like structure composed mainly of DNA and citrullinated histones, called neutrophil extracellular traps (NET) that modify the stability and lysability of fibrin. Here, we investigated the NET-related structural features of thrombi retrieved from different arterial localizatio...
3 CitationsSource
#1Amr A. Al-HaidariH-Index: 5
#2Nader AlgethamiH-Index: 1
Last. Henrik ThorlaciusH-Index: 36
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Cytoreductive surgery is the only curative option for patients with peritoneal carcinomatosis, however, intraperitoneal recurrence rate is high making new ways to prevent cancer recurrence an urgent need. Recent evidence suggests that neutrophils are involved in cancer progression. The purpose of our study was to examine the role of neutrophils in the spread of colon cancer cells in the peritoneal cavity. The number of metastatic noduli in the peritoneal cavity was quantified in mice injected wi...
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#1Ludwig T. WeckbachH-Index: 9
#2Ulrich Grabmaier (LMU: Ludwig Maximilian University of Munich)H-Index: 9
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Heart failure due to dilated cardiomyopathy is frequently caused by myocarditis. However, the pathogenesis of myocarditis remains incompletely understood. Here, we report the presence of neutrophil extracellular traps (NETs) in cardiac tissue of patients and mice with myocarditis. Inhibition of NET formation in experimental autoimmune myocarditis (EAM) of mice substantially reduces inflammation in the acute phase of the disease. Targeting the cytokine midkine (MK), which mediates NET formation i...
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Neutrophil extracellular traps (NETs) are web-like DNA structures decorated with histones and cytotoxic proteins that are released by activated neutrophils to trap and neutralize pathogens during the innate immune response, but also form in and exacerbate sterile inflammation. Peptidylarginine deiminase 4 (PAD4) citrullinates histones and is required for NET formation (NETosis) in mouse neutrophils. While the in vivo impact of NETs is accumulating, the cellular events driving NETosis and the rol...
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Resumen Los neutrofilos, cuando son activados, liberan estructuras (NETs) compuestas por ADN, histonas y proteinas granulares que proporcionan una matriz idonea para la activacion plaquetaria y de los mecanismos de coagulacion, contribuyendo asi a la patogenia de la trombosis en los territorios venoso y arterial, asi como a la trombosis asociada a cancer. Los NETs desempenan un papel clave en la inmunotrombosis, termino que describe la relacion entre la respuesta inmune y la coagulacion.
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Neutrophil extracellular traps (NETs) are formed by decondensed chromatin, histones, and neutrophil granular proteins and have a role in entrapping microbial pathogens. NETs, however, have pro-thrombotic properties by stimulating fibrin deposition, and increased NET levels correlate with larger infarct size and predict major adverse cardiovascular (CV) events. NETs have been involved also in the pathogenesis of diabetes, as high glucose levels were found to induce NETosis. Accordingly, NETs have...
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Abstract The innate and adaptive immune mechanisms are key components of regulation of reproductive physiological function and uterine disorders in equine uterus. The predominant immunological response in equine endometrium, characterized by an innate immune response, occurs under estrogens influence, in the follicular phase. Although, the increase in immune-related genes in equine endometrium during estrus has been suggested to play a role in uterine clearance after mating, immune cells and the...
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