scholarly journals Synthetic Siglec-9 Agonists Inhibit Neutrophil Activation Associated with COVID-19

2020 ◽  
Author(s):  
Corleone Delaveris ◽  
Aaron Wilk ◽  
Nicholas Riley ◽  
Jessica Stark ◽  
Samuel Yang ◽  
...  
Keyword(s):  
Immune Response ◽  
Therapeutic Strategy ◽  
Neutrophil Extracellular Traps ◽  
Neutrophil Activation ◽  
Signaling Cascade ◽  
Peripheral Inflammation ◽  
Pulmonary Tissue ◽  
Extracellular Traps ◽  
Cell Death Pathway ◽  
Key Factor

Severe cases of coronavirus disease 2019 (COVID-19), caused by infection with SARS-Cov-2, are characterized by a hyperinflammatory immune response that leads to numerous complications. Production of proinflammatory neutrophil extracellular traps (NETs) has been suggested to be a key factor in inducing a hyperinflammatory signaling cascade, allegedly causing both pulmonary tissue damage and peripheral inflammation. Accordingly, therapeutic blockage of neutrophil activation and NETosis, the cell death pathway accompanying NET formation, could limit respiratory damage and death from severe COVID-19. Here, we demonstrate that synthetic glycopolymers that activate the neutrophil checkpoint receptor Siglec-9 suppress NETosis induced by agonists of viral toll-like receptors (TLRs) and plasma from patients with severe COVID-19. Thus, Siglec-9 agonism is a promising therapeutic strategy to curb neutrophilic hyperinflammation in COVID-19.<br>

scholarly journals Synthetic Siglec-9 Agonists Inhibit Neutrophil Activation Associated with COVID-19

2020 ◽  
Author(s):  
Corleone Delaveris ◽  
Aaron Wilk ◽  
Nicholas Riley ◽  
Jessica Stark ◽  
Samuel Yang ◽  
...  
Keyword(s):  
Immune Response ◽  
Therapeutic Strategy ◽  
Neutrophil Extracellular Traps ◽  
Neutrophil Activation ◽  
Signaling Cascade ◽  
Peripheral Inflammation ◽  
Pulmonary Tissue ◽  
Extracellular Traps ◽  
Cell Death Pathway ◽  
Key Factor

Severe cases of coronavirus disease 2019 (COVID-19), caused by infection with SARS-Cov-2, are characterized by a hyperinflammatory immune response that leads to numerous complications. Production of proinflammatory neutrophil extracellular traps (NETs) has been suggested to be a key factor in inducing a hyperinflammatory signaling cascade, allegedly causing both pulmonary tissue damage and peripheral inflammation. Accordingly, therapeutic blockage of neutrophil activation and NETosis, the cell death pathway accompanying NET formation, could limit respiratory damage and death from severe COVID-19. Here, we demonstrate that synthetic glycopolymers that activate the neutrophil checkpoint receptor Siglec-9 suppress NETosis induced by agonists of viral toll-like receptors (TLRs) and plasma from patients with severe COVID-19. Thus, Siglec-9 agonism is a promising therapeutic strategy to curb neutrophilic hyperinflammation in COVID-19.<br>

scholarly journals Silver Nanoparticles Induce Neutrophil Extracellular Traps Via Activation of PAD and Neutrophil Elastase

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 317
Author(s):  
HanGoo Kang ◽  
Jinwon Seo ◽  
Eun-Jeong Yang ◽  
In-Hong Choi
Keyword(s):  
Silver Nanoparticles ◽  
Neutrophil Elastase ◽  
Mammalian Cells ◽  
Antimicrobial Properties ◽  
Neutrophil Extracellular Traps ◽  
Arginine Deiminase ◽  
Human Neutrophils ◽  
Extracellular Traps ◽  
Peptidyl Arginine Deiminase ◽  
Key Factor

Silver nanoparticles (AgNPs) are widely used in various fields because of their antimicrobial properties. However, many studies have reported that AgNPs can be harmful to both microorganisms and humans. Reactive oxygen species (ROS) are a key factor of cytotoxicity of AgNPs in mammalian cells and an important factor in the immune reaction of neutrophils. The immune reactions of neutrophils include the expulsion of webs of DNA surrounded by histones and granular proteins. These webs of DNA are termed neutrophil extracellular traps (NETs). NETs allow neutrophils to catch and destroy pathogens in extracellular spaces. In this study, we investigated how AgNPs stimulate neutrophils, specifically focusing on NETs. Freshly isolated human neutrophils were treated with 5 or 100 nm AgNPs. The 5 nm AgNPs induced NET formation, but the 100 nm AgNPs did not. Subsequently, we investigated the mechanism of AgNP-induced NETs using known inhibitors related to NET formation. AgNP-induced NETs were dependent on ROS, peptidyl arginine deiminase, and neutrophil elastase. The result in this study indicates that treatment of 5 nm AgNPs induce NET formation through histone citrullination by peptidyl arginine deiminase and histone cleavage by neutrophil elastase.

scholarly journals Prognostic value of circulating markers of neutrophil activation, neutrophil extracellular traps, coagulation and fibrinolysis in patients with terminal cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Axel Rosell ◽  
Katherina Aguilera ◽  
Yohei Hisada ◽  
Clare Schmedes ◽  
Nigel Mackman ◽  
...  
Keyword(s):  
Advanced Cancer ◽  
Prognostic Value ◽  
Neutrophil Extracellular Traps ◽  
Neutrophil Activation ◽  
Terminal Cancer ◽  
Extracellular Traps ◽  
Terminal Cancer Patients ◽  
Future Care ◽  
Circulating Markers ◽  
Coagulation And Fibrinolysis

AbstractPredicting survival accurately in patients with advanced cancer is important in guiding interventions and planning future care. Objective tools are therefore needed. Blood biomarkers are appealing due to their rapid measurement and objective nature. Thrombosis is a common complication in cancer. Recent data indicate that tumor-induced neutrophil extracellular traps (NETs) are pro-thrombotic. We therefore performed a comprehensive investigation of circulating markers of neutrophil activation, NET formation, coagulation and fibrinolysis in 106 patients with terminal cancer. We found that neutrophil activation and NET markers were prognostic in terminal cancer patients. Interestingly, markers of coagulation and fibrinolysis did not have a prognostic value in this patient group, and there were weak or no correlations between these markers and markers of neutrophil activation and NETs. This suggest that NETs are linked to a poor prognosis through pathways independent of coagulation. Additional studies are needed to determine the utility of circulating neutrophil activation and NET markers, alone or in concert with established clinical parameters, as objective and reliable prognostic tools in advanced cancer.

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 (NETs) and Damage-Associated Molecular Patterns (DAMPs): Two Potential Targets for COVID-19 Treatment

2020 ◽  
Vol 2020 ◽  
pp. 1-25 ◽  
Author(s):  
Sebastiano Cicco ◽  
Gerolamo Cicco ◽  
Vito Racanelli ◽  
Angelo Vacca
Keyword(s):  
Immune Response ◽  
Innate Immunity ◽  
Targeted Therapy ◽  
High Mobility ◽  
Neutrophil Extracellular Traps ◽  
Lung Cells ◽  
Extracellular Traps ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns ◽  
Excessive Inflammatory Response

COVID-19 is a pandemic disease caused by the new coronavirus SARS-CoV-2 that mostly affects the respiratory system. The consequent inflammation is not able to clear viruses. The persistent excessive inflammatory response can build up a clinical picture that is very difficult to manage and potentially fatal. Modulating the immune response plays a key role in fighting the disease. One of the main defence systems is the activation of neutrophils that release neutrophil extracellular traps (NETs) under the stimulus of autophagy. Various molecules can induce NETosis and autophagy; some potent activators are damage-associated molecular patterns (DAMPs) and, in particular, the high-mobility group box 1 (HMGB1). This molecule is released by damaged lung cells and can induce a robust innate immunity response. The increase in HMGB1 and NETosis could lead to sustained inflammation due to SARS-CoV-2 infection. Therefore, blocking these molecules might be useful in COVID-19 treatment and should be further studied in the context of targeted therapy.

scholarly journals Novel cell death program leads to neutrophil extracellular traps

2007 ◽  
Vol 176 (2) ◽  
pp. 231-241 ◽  
Author(s):  
Tobias A. Fuchs ◽  
Ulrike Abed ◽  
Christian Goosmann ◽  
Robert Hurwitz ◽  
Ilka Schulze ◽  
...  
Keyword(s):  
Cell Death ◽  
Nadph Oxidase ◽  
Neutrophil Extracellular Traps ◽  
Death Process ◽  
Extracellular Traps ◽  
Cell Death Pathway ◽  
Antimicrobial Function ◽  
Cell Death Program ◽  
Cell Death Process ◽  
Extracellular Structures

Neutrophil extracellular traps (NETs) are extracellular structures composed of chromatin and granule proteins that bind and kill microorganisms. We show that upon stimulation, the nuclei of neutrophils lose their shape, and the eu- and heterochromatin homogenize. Later, the nuclear envelope and the granule membranes disintegrate, allowing the mixing of NET components. Finally, the NETs are released as the cell membrane breaks. This cell death process is distinct from apoptosis and necrosis and depends on the generation of reactive oxygen species (ROS) by NADPH oxidase. Patients with chronic granulomatous disease carry mutations in NADPH oxidase and cannot activate this cell-death pathway or make NETs. This novel ROS-dependent death allows neutrophils to fulfill their antimicrobial function, even beyond their lifespan.

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