scholarly journals Neutrophil Extracellular Traps Affecting Cardiovascular Health in Infectious and Inflammatory Diseases

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1689
Author(s):  
Manovriti Thakur ◽  
Bryce Evans ◽  
Marc Schindewolf ◽  
Iris Baumgartner ◽  
Yvonne Döring

Neutrophil extracellular traps (NETs) are web-like structures of decondensed extracellular chromatin fibers and neutrophil granule proteins released by neutrophils. NETs participate in host immune defense by entrapping pathogens. They are pro-inflammatory in function, and they act as an initiator of vascular coagulopathies by providing a platform for the attachment of various coagulatory proteins. NETs are diverse in their ability to alter physiological and pathological processes including infection and inflammation. In this review, we will summarize recent findings on the role of NETs in bacterial/viral infections associated with vascular inflammation, thrombosis, atherosclerosis and autoimmune disorders. Understanding the complex role of NETs in bridging infection and chronic inflammation as well as discussing important questions related to their contribution to pathologies outlined above may pave the way for future research on therapeutic targeting of NETs applicable to specific infections and inflammatory disorders.

2021 ◽  
Vol 8 (4) ◽  
pp. 275-290
Author(s):  
Amal Feiroze Farouk ◽  
◽  
Areez Shafqat ◽  
Shameel Shafqat ◽  
Junaid Kashir ◽  
...  

<abstract> <p>The COVID-19 pandemic has driven an upheaval of new research, providing key insights into the pathogenesis of this disease. Lymphocytopenia, hyper-inflammation and cardiac involvement are prominent features of the disease and have prognostic value. However, the mechanistic links among these phenomena are not well understood. Likewise, some COVID-19 patients exhibit multi-organ failure with diseases affecting the cardiac system, appearing to be an emerging feature of the COVID-19 pandemic. Neutrophil extracellular traps (NETs) have been frequently correlated with larger infarct sizes and can predict major adverse cardiac events. However, the exact mechanism behind this remains unknown. Although the excessive NET formation can drive inflammation, particularly endothelial and promote thrombosis, it is essential to normal immunity. In this paper, we postulate the role of NETs in cardiac disease by providing an overview of the relationship between NET and inflammasome activities in lung and liver diseases, speculating a link between these entities in cardiac diseases as well. Future research is required to specify the role of NETs in COVID-19, since this carries potential therapeutic significance, as inhibition of NETosis could alleviate symptoms of this disease. Knowledge gained from this could serve to inform the assessment and therapeutics of other hyper inflammatory diseases affecting the heart and vasculature alike.</p> </abstract>


2021 ◽  
Vol 22 (16) ◽  
pp. 8854
Author(s):  
Monika Szturmowicz ◽  
Urszula Demkow

Neutrophil extracellular traps (NETs), built from mitochondrial or nuclear DNA, proteinases, and histones, entrap and eliminate pathogens in the course of bacterial or viral infections. Neutrophils’ activation and the formation of NETs have been described as major risk factors for acute lung injury, multi-organ damage, and mortality in COVID-19 disease. NETs-related lung injury involves both epithelial and endothelial cells, as well as the alveolar-capillary barrier. The markers for NETs formation, such as circulating DNA, neutrophil elastase (NE) activity, or myeloperoxidase-DNA complexes, were found in lung specimens of COVID-19 victims, as well as in sera and tracheal aspirates obtained from COVID-19 patients. DNA threads form large conglomerates causing local obstruction of the small bronchi and together with NE are responsible for overproduction of mucin by epithelial cells. Various components of NETs are involved in the pathogenesis of cytokine storm in SARS-CoV-2 pulmonary disease. NETs are responsible for the interplay between inflammation and thrombosis in the affected lungs. The immunothrombosis, stimulated by NETs, has a poor prognostic significance. Better understanding of the role of NETs in the course of COVID-19 can help to develop novel approaches to the therapeutic interventions in this condition.


2014 ◽  
Vol 112 (10) ◽  
pp. 659-665 ◽  
Author(s):  
Robert Andrews ◽  
Jane Arthur ◽  
Elizabeth Gardiner

SummaryIn addition to playing a central role in normal haemostasis, platelets make important contributions to host inflammatory and immune responses to injury or infection. Under pathophysiological conditions where platelet function is not tightly controlled, platelets also play critical roles in pathogenic processes underlying cardiovascular disease, uncontrolled inflammation, coagulopathy and in tumour metastasis. Neutrophil extracellular traps (NETs) are webs of histone-modified nuclear material extruded from activated neutrophils during inflammatory responses and these degranulation events can be directly triggered by platelet/neutrophil engagement. Emerging research describes how NETs influence platelet function, particularly in the setting of infection and inflammation. Especially intriguing is the potential for platelet-driven coagulation to be modulated by NETs in plasma and interstitial spaces. These findings also reveal new perspectives related to improved therapy for venous thrombosis.


2020 ◽  
Vol 217 (12) ◽  
Author(s):  
Flavio Protasio Veras ◽  
Marjorie Cornejo Pontelli ◽  
Camila Meirelles Silva ◽  
Juliana E. Toller-Kawahisa ◽  
Mikhael de Lima ◽  
...  

Severe COVID-19 patients develop acute respiratory distress syndrome that may progress to cytokine storm syndrome, organ dysfunction, and death. Considering that neutrophil extracellular traps (NETs) have been described as important mediators of tissue damage in inflammatory diseases, we investigated whether NETs would be involved in COVID-19 pathophysiology. A cohort of 32 hospitalized patients with a confirmed diagnosis of COVID-19 and healthy controls were enrolled. The concentration of NETs was augmented in plasma, tracheal aspirate, and lung autopsies tissues from COVID-19 patients, and their neutrophils released higher levels of NETs. Notably, we found that viable SARS-CoV-2 can directly induce the release of NETs by healthy neutrophils. Mechanistically, NETs triggered by SARS-CoV-2 depend on angiotensin-converting enzyme 2, serine protease, virus replication, and PAD-4. Finally, NETs released by SARS-CoV-2–activated neutrophils promote lung epithelial cell death in vitro. These results unravel a possible detrimental role of NETs in the pathophysiology of COVID-19. Therefore, the inhibition of NETs represents a potential therapeutic target for COVID-19.


2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Sultan Z. Alasmari

Neutrophils comprise the first line of innate immune defense during a host-pathogen interaction. They attack microorganisms directly through three different methods, of which, phagocytosis and degranulation have been known and well-studied for decades. The formation of neutrophil extracellular traps (NETs) is the third and unique method, which was unveiled in 2004. Since then, many studies on NETs have been carried out. However, only few have successfully demonstrated the activity of NETs in vivo. Results of the in vivo studies on NETs have strengthened our understanding of their role in different situations. This review highlights the main in vivo studies, which have contributed in extending our understanding of the role of NETs during infections and diseases, thus indicating their advantages and limitations.


2019 ◽  
pp. 1-9 ◽  
Author(s):  
Quratul Ann

Neutrophils are an integral part of innate immune response system, abundantly present in blood circulation. They are the primary responders to the injury or intruding pathogens in human body. Neutrophils engulf infectious microorganisms by the process of phagocytosis, which usually initiates the production of reactive oxygen species and adhere the neutrophilic antimicrobial granules with vacuoles containing pathogens. Upon activation, neutrophils also render signals for stimulation and maturation of macrophages and dendritic cells. They release neutrophil extracellular traps for the suppression of infection and inflammation along with other antimicrobial molecules. The antimicrobials that are present in neutrophil extracellular traps not only eradicate microbes but also moderately contribute to the pathogenesis of various diseases such as destruction of tissue observed in periodontitis. Genetic shortcomings in neutrophils with respect to their chemotaxis, migration and phagocytosis become evident as severe forms of periodontitis, thus highlighting their role in innate immunity. Therefore, the present review is undertaken to highlight the importance of production and release of neutrophil extracellular trap in the regulation of immune reaction and its role in periodontal disease. A comprehensive database search was performed to gather all the relevant data related to the action of neutrophil and neutrophil extracellular traps in various inflammatory diseases with special emphasis on periodontitis.


Medicina ◽  
2019 ◽  
Vol 55 (8) ◽  
pp. 431 ◽  
Author(s):  
Hector Salazar-Gonzalez ◽  
Alexa Zepeda-Hernandez ◽  
Zesergio Melo ◽  
Diego Eduardo Saavedra-Mayorga ◽  
Raquel Echavarria

Uncontrolled inflammatory and immune responses are often involved in the development of acute and chronic forms of renal injury. Neutrophils are innate immune cells recruited early to sites of inflammation, where they produce pro-inflammatory cytokines and release mesh-like structures comprised of DNA and granular proteins known as neutrophil extracellular traps (NETs). NETs are potentially toxic, contribute to glomerular injury, activate autoimmune processes, induce vascular damage, and promote kidney fibrosis. Evidence from multiple studies suggests that an imbalance between production and clearance of NETs is detrimental for renal health. Hence strategies aimed at modulating NET-associated processes could have a therapeutic impact on a myriad of inflammatory diseases that target the kidney. Here, we summarize the role of NETs in the pathogenesis of renal diseases and their mechanisms of tissue damage.


Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1469
Author(s):  
Carolina Domínguez-Díaz ◽  
Gael Urait Varela-Trinidad ◽  
Germán Muñoz-Sánchez ◽  
Karla Solórzano-Castanedo ◽  
Karina Elizabeth Avila-Arrezola ◽  
...  

Neutrophils are the most abundant circulating innate immune cells and comprise the first immune defense line, as they are the most rapidly recruited cells at sites of infection or inflammation. Their main microbicidal mechanisms are degranulation, phagocytosis, cytokine secretion and the formation of extracellular traps. Neutrophil extracellular traps (NETs) are a microbicidal mechanism that involves neutrophil death. Since their discovery, in vitro and in vivo neutrophils have been challenged with a range of stimuli capable of inducing or inhibiting NET formation, with the objective to understand its function and regulation in health and disease. These networks composed of DNA and granular components are capable of immobilizing and killing pathogens. They comprise enzymes such as myeloperoxidase, elastase, cathepsin G, acid hydrolases and cationic peptides, all with antimicrobial and antifungal activity. Therefore, the excessive formation of NETs can also lead to tissue damage and promote local and systemic inflammation. Based on this concept, in this review, we focus on the role of NETs in different infectious and inflammatory diseases of the mucosal epithelia and skin.


2018 ◽  
Vol 118 (01) ◽  
pp. 006-027 ◽  
Author(s):  
Aldo Bonaventura ◽  
Luca Liberale ◽  
Federico Carbone ◽  
Alessandra Vecchié ◽  
Candela Diaz-Cañestro ◽  
...  

AbstractNeutrophil pathogen-killing mechanism termed neutrophil extracellular traps (NETs) has been recently identified. NETs consist of chromatin and histones along with serine proteases and myeloperoxidase and are induced by a great variety of infectious and non-infectious stimuli. NETosis is a kind of programmed neutrophil death characterized by chromatin decondensation and release of nuclear granular contents, mainly driven by peptidylarginine deiminase 4 citrullination of histones. Although classically related to the protection against infectious pathogens, nowadays NETs have been described as a player of several pathophysiological processes. Neutrophil dysregulation has been demonstrated in the pathogenesis of most representative vascular diseases, such as acute coronary syndrome, stroke and venous thrombosis. Indeed, NETs have been identified within atherosclerotic lesions and arterial thrombi in both human beings and animal models. Moreover, an imbalance in this mechanism has been proposed as a critical source of modified and/or externalized autoantigens in autoimmune and inflammatory diseases. Finally, an update on the role of NETs in the pathogenesis of cancer has been included. In the present review, based on papers released on PubMed and MEDLINE up to July 2017, we point to update the knowledge on NETs, from their structure to their roles in infectious diseases as well as in cardiovascular diseases, autoimmunity, metabolic disorders and cancer, with a look to future perspectives and therapeutic opportunities.


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