scholarly journals Neutrophil Extracellular Traps: Current Perspectives in the Eye

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 979 ◽  
Author(s):  
Gibrán Alejandro Estúa-Acosta ◽  
Rocío Zamora-Ortiz ◽  
Beatriz Buentello-Volante ◽  
Mariana García-Mejía ◽  
Yonathan Garfias
Keyword(s):  
Innate Immunity ◽  
Neutrophil Extracellular Traps ◽  
Current Data ◽  
Eye Diseases ◽  
Pathogenic Microorganisms ◽  
Extracellular Traps ◽  
Wide Range ◽  
Decondensed Chromatin ◽  
The Subject ◽  
Granule Proteins

Neutrophil extracellular traps (NETs) have been the subject of research in the field of innate immunity since their first description more than a decade ago. Neutrophils are the first cells recruited at sites of inflammation, where they perform their specific functions, including the release of NETs, which consist of web-like structures composed of granule proteins bound to decondensed chromatin fibres. This process has aroused interest, as it contributes to understanding how pathogenic microorganisms are contained, but they are also associated with pathophysiological processes of a wide range of diseases. Currently, there are growing reports of new molecules involved in the formation and release of NETs. However, whether the release of NETs contributes to eye diseases remains unclear. For this reason, the overall aim of this review is to gather current data of recent research in the ophthalmology field, where there is still much to discover.

scholarly journals PAD4 is essential for antibacterial innate immunity mediated by neutrophil extracellular traps

2010 ◽  
Vol 207 (9) ◽  
pp. 1853-1862 ◽  
Author(s):  
Pingxin Li ◽  
Ming Li ◽  
Michael R. Lindberg ◽  
Mary J. Kennett ◽  
Na Xiong ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Bacterial Infection ◽  
Disease Model ◽  
Neutrophil Extracellular Traps ◽  
Chromatin Decondensation ◽  
Bacterial Killing ◽  
Infectious Disease Model ◽  
Extracellular Traps ◽  
Decondensed Chromatin

Neutrophils trap and kill bacteria by forming highly decondensed chromatin structures, termed neutrophil extracellular traps (NETs). We previously reported that histone hypercitrullination catalyzed by peptidylarginine deiminase 4 (PAD4) correlates with chromatin decondensation during NET formation. However, the role of PAD4 in NET-mediated bacterial trapping and killing has not been tested. Here, we use PAD4 knockout mice to show that PAD4 is essential for NET-mediated antibacterial function. Unlike PAD4+/+ neutrophils, PAD4−/− neutrophils cannot form NETs after stimulation with chemokines or incubation with bacteria, and are deficient in bacterial killing by NETs. In a mouse infectious disease model of necrotizing fasciitis, PAD4−/− mice are more susceptible to bacterial infection than PAD4+/+ mice due to a lack of NET formation. Moreover, we found that citrullination decreased the bacterial killing activity of histones and nucleosomes, which suggests that PAD4 mainly plays a role in chromatin decondensation to form NETs instead of increasing histone-mediated bacterial killing. Our results define a role for histone hypercitrullination in innate immunity during bacterial infection.

scholarly journals Neutrophil elastase and myeloperoxidase regulate the formation of neutrophil extracellular traps

2010 ◽  
Vol 191 (3) ◽  
pp. 677-691 ◽  
Author(s):  
Venizelos Papayannopoulos ◽  
Kathleen D. Metzler ◽  
Abdul Hakkim ◽  
Arturo Zychlinsky
Keyword(s):  
Immune Deficiency ◽  
Neutrophil Elastase ◽  
Serine Proteases ◽  
Neutrophil Extracellular Traps ◽  
Oxygen Species ◽  
Chromatin Decondensation ◽  
Unknown Mechanism ◽  
Extracellular Traps ◽  
Decondensed Chromatin ◽  
Chromatin Density

Neutrophils release decondensed chromatin termed neutrophil extracellular traps (NETs) to trap and kill pathogens extracellularly. Reactive oxygen species are required to initiate NET formation but the downstream molecular mechanism is unknown. We show that upon activation, neutrophil elastase (NE) escapes from azurophilic granules and translocates to the nucleus, where it partially degrades specific histones, promoting chromatin decondensation. Subsequently, myeloperoxidase synergizes with NE in driving chromatin decondensation independent of its enzymatic activity. Accordingly, NE knockout mice do not form NETs in a pulmonary model of Klebsiella pneumoniae infection, which suggests that this defect may contribute to the immune deficiency of these mice. This mechanism provides for a novel function for serine proteases and highly charged granular proteins in the regulation of chromatin density, and reveals that the oxidative burst induces a selective release of granular proteins into the cytoplasm through an unknown mechanism.

NETosis: how vital is it?

Blood ◽  
2013 ◽  
Vol 122 (16) ◽  
pp. 2784-2794 ◽  
Author(s):  
Bryan G. Yipp ◽  
Paul Kubes
Keyword(s):  
Innate Immunity ◽  
Cell Death ◽  
Critical Role ◽  
Neutrophil Extracellular Traps ◽  
Live Cell ◽  
Extracellular Traps ◽  
Cell Death Pathway ◽  
A Cell ◽  
Net Release

Abstract In this review, we examine the evidence that neutrophil extracellular traps (NETs) play a critical role in innate immunity. We summarize how NETs are formed in response to various stimuli and provide evidence that NETosis is not universally a cell death pathway. Here we describe at least 2 different mechanisms by which NETs are formed, including a suicide lytic NETosis and a live cell or vital NETosis. We also evaluate the evidence for NETs in catching and killing pathogens. Finally, we examine how infections are related to the development of autoimmune and vasculitic diseases through unintended but detrimental bystander damage resulting from NET release.

scholarly journals Neutrophil Extracellular Traps in Periodontitis

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1494 ◽  
Author(s):  
Antonio Magán-Fernández ◽  
Sarmad Muayad Rasheed Al-Bakri ◽  
Francisco O’Valle ◽  
Cristina Benavides-Reyes ◽  
Francisco Abadía-Molina ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Decisive Role ◽  
Neutrophil Extracellular Traps ◽  
Gingival Tissue ◽  
Multifactorial Disease ◽  
Extracellular Traps ◽  
Wide Range ◽  
Neutrophil Response ◽  
Inflammatory Component

Neutrophils are key cells of the immune system and have a decisive role in fighting foreign pathogens in infectious diseases. Neutrophil extracellular traps (NETs) consist of a mesh of DNA enclosing antimicrobial peptides and histones that are released into extracellular space following neutrophil response to a wide range of stimuli, such as pathogens, host-derived mediators and drugs. Neutrophils can remain functional after NET formation and are important for periodontal homeostasis. Periodontitis is an inflammatory multifactorial disease caused by a dysbiosis state between the gingival microbiome and the immune response of the host. The pathogenesis of periodontitis includes an immune-inflammatory component in which impaired NET formation and/or elimination can be involved, contributing to an exacerbated inflammatory reaction and to the destruction of gingival tissue. In this review, we summarize the current knowledge about the role of NETs in the pathogenesis of periodontitis.

scholarly journals The humoral pattern recognition receptor PTX3 is stored in neutrophil granules and localizes in extracellular traps

2007 ◽  
Vol 204 (4) ◽  
pp. 793-804 ◽  
Author(s):  
Sébastien Jaillon ◽  
Giuseppe Peri ◽  
Yves Delneste ◽  
Isabelle Frémaux ◽  
Andrea Doni ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Neutrophil Extracellular Traps ◽  
Toll Like Receptor ◽  
Myeloid Dendritic Cells ◽  
Opsonic Activity ◽  
Extracellular Traps ◽  
Inflammatory Signals ◽  
Rapid Release ◽  
Specific Granules ◽  
Recognition Receptor

The long pentraxin (PTX) 3 is produced by macrophages and myeloid dendritic cells in response to Toll-like receptor agonists and represents a nonredundant component of humoral innate immunity against selected pathogens. We report that, unexpectedly, PTX3 is stored in specific granules and undergoes release in response to microbial recognition and inflammatory signals. Released PTX3 can partially localize in neutrophil extracellular traps formed by extruded DNA. Eosinophils and basophils do not contain preformed PTX3. PTX3-deficient neutrophils have defective microbial recognition and phagocytosis, and PTX3 is nonredundant for neutrophil-mediated resistance against Aspergillus fumigatus. Thus, neutrophils serve as a reservoir, ready for rapid release, of the long PTX3, a key component of humoral innate immunity with opsonic activity.

scholarly journals Heparan Sulfate Modulates Neutrophil and Endothelial Function in Antibacterial Innate Immunity

2015 ◽  
Vol 83 (9) ◽  
pp. 3648-3656 ◽  
Author(s):  
Ding Xu ◽  
Joshua Olson ◽  
Jason N. Cole ◽  
Xander M. van Wijk ◽  
Volker Brinkmann ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Heparan Sulfate ◽  
Bactericidal Activity ◽  
Bacterial Pathogen ◽  
Systemic Infection ◽  
Neutrophil Extracellular Traps ◽  
Content Type ◽  
Extracellular Traps ◽  
The Central Nervous System ◽  
Group B

Recently, we showed that endothelial heparan sulfate facilitates entry of a bacterial pathogen into the central nervous system. Here, we show that normal bactericidal activity of neutrophils is influenced by the sulfation pattern of heparan sulfate. Inactivation of heparan sulfate uronyl 2-O-sulfotransferase (Hs2st) in neutrophils substantially reduced their bactericidal activity, and Hs2st deficiency rendered mice more susceptible to systemic infection with the pathogenic bacterium group BStreptococcus. Specifically, altered sulfation of heparan sulfate in mutant neutrophils affected formation of neutrophil extracellular traps while not influencing phagocytosis, production of reactive oxygen species, or secretion of granular proteases. Heparan sulfate proteoglycan(s) is present in neutrophil extracellular traps, modulates histone affinity, and modulates their microbial activity. Hs2st-deficient brain endothelial cells show enhanced binding to group BStreptococcusand are more susceptible to apoptosis, likely contributing to the observed increase in dissemination of group BStreptococcusinto the brain of Hs2st-deficient mice following intravenous challenge. Taken together, our data provide strong evidence that heparan sulfate from both neutrophils and the endothelium plays important roles in modulating innate immunity.

scholarly journals Evidence against the microbicidal action of neutrophil extracellular traps (NETs)

2018 ◽  
Author(s):  
F. Semplici ◽  
A. W. Segal
Keyword(s):  
Neutrophil Elastase ◽  
Dna Structure ◽  
Neutrophil Extracellular Traps ◽  
Cathepsin G ◽  
Nuclear Chromatin ◽  
Extracellular Traps ◽  
Granule Proteins ◽  
Bacteria And Fungi

AbstractNeutrophil extracellular traps (NETs) are fibrillary structures composed of extruded nuclear chromatin decorated with granule proteins (mostly neutrophil elastase, cathepsin G and myeloperoxidase). It has been reported that NETs are able to kill bacteria and fungi based upon the observation that smaller number of organisms are obtained in plating assays after they are incubated with NETs than if the DNA is pre-digested with DNase. It is possible that the microbial killing is apparent rather than real, and occurs because the organisms are aggregated on the DNA structure, and that the plating assay results were simply misinterpreted. The present study shows that digestion of DNA after incubation of NETs with the microbes restores their numbers to preincubation levels indicating that the apparent killing is an artefact of the assay.

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