scholarly journals The Pathophysiological Role of Neutrophil Extracellular Traps in Inflammatory Diseases

2018 ◽  
Vol 118 (01) ◽  
pp. 006-027 ◽  
Author(s):  
Aldo Bonaventura ◽  
Luca Liberale ◽  
Federico Carbone ◽  
Alessandra Vecchié ◽  
Candela Diaz-Cañestro ◽  
...  
Keyword(s):  
Serine Proteases ◽  
Inflammatory Diseases ◽  
Vascular Diseases ◽  
Neutrophil Extracellular Traps ◽  
Human Beings ◽  
Coronary Syndrome ◽  
Extracellular Traps ◽  
Atherosclerotic Lesions ◽  
Autoimmune And Inflammatory Diseases

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.

scholarly journals SARS-CoV-2–triggered neutrophil extracellular traps mediate COVID-19 pathology

2020 ◽  
Vol 217 (12) ◽  
Author(s):  
Flavio Protasio Veras ◽  
Marjorie Cornejo Pontelli ◽  
Camila Meirelles Silva ◽  
Juliana E. Toller-Kawahisa ◽  
Mikhael de Lima ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Tracheal Aspirate ◽  
Neutrophil Extracellular Traps ◽  
Angiotensin Converting Enzyme 2 ◽  
Extracellular Traps ◽  
Lung Epithelial ◽  
Activated Neutrophils ◽  
Epithelial Cell Death

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.

scholarly journals The Dual Role of Myeloperoxidase in Immune Response

2020 ◽  
Vol 21 (21) ◽  
pp. 8057 ◽  
Author(s):  
Jürgen Arnhold
Keyword(s):  
Immune Response ◽  
Innate Immune System ◽  
Neutrophil Extracellular Traps ◽  
Innate Immune ◽  
Major Constituent ◽  
Extracellular Traps ◽  
Atherosclerotic Lesions ◽  
Disease Specific ◽  
Frustrated Phagocytosis

The heme protein myeloperoxidase (MPO) is a major constituent of neutrophils. As a key mediator of the innate immune system, neutrophils are rapidly recruited to inflammatory sites, where they recognize, phagocytose, and inactivate foreign microorganisms. In the newly formed phagosomes, MPO is involved in the creation and maintenance of an alkaline milieu, which is optimal in combatting microbes. Myeloperoxidase is also a key component in neutrophil extracellular traps. These helpful properties are contrasted by the release of MPO and other neutrophil constituents from necrotic cells or as a result of frustrated phagocytosis. Although MPO is inactivated by the plasma protein ceruloplasmin, it can interact with negatively charged components of serum and the extracellular matrix. In cardiovascular diseases and many other disease scenarios, active MPO and MPO-modified targets are present in atherosclerotic lesions and other disease-specific locations. This implies an involvement of neutrophils, MPO, and other neutrophil products in pathogenesis mechanisms. This review critically reflects on the beneficial and harmful functions of MPO against the background of immune response.

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
Keyword(s):  
Cardiovascular Health ◽  
Viral Infections ◽  
Inflammatory Diseases ◽  
Vascular Inflammation ◽  
Neutrophil Extracellular Traps ◽  
Immune Defense ◽  
Future Research ◽  
Extracellular Traps ◽  
Infection And Inflammation

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.

scholarly journals Neutrophil Extracellular Traps in the Establishment and Progression of Renal Diseases

Medicina ◽  
2019 ◽  
Vol 55 (8) ◽  
pp. 431 ◽  
Author(s):  
Hector Salazar-Gonzalez ◽  
Alexa Zepeda-Hernandez ◽  
Zesergio Melo ◽  
Diego Eduardo Saavedra-Mayorga ◽  
Raquel Echavarria
Keyword(s):  
Inflammatory Diseases ◽  
Neutrophil Extracellular Traps ◽  
Innate Immune ◽  
Renal Diseases ◽  
Glomerular Injury ◽  
Kidney Fibrosis ◽  
Extracellular Traps ◽  
Autoimmune Processes ◽  
Pro Inflammatory Cytokines

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.

The Role of Interleukin-27 in Atherosclerosis: A Contemporary Review

Cardiology ◽  
2021 ◽  
pp. 1-13
Author(s):  
Mehrian Jafarizade ◽  
Farima Kahe ◽  
Sadaf Sharfaei ◽  
Kaveh Momenzadeh ◽  
Anmol Pitliya ◽  
...  
Keyword(s):  
Vascular Endothelium ◽  
Inflammatory Diseases ◽  
Atherosclerotic Plaques ◽  
Future Studies ◽  
Coronary Syndrome ◽  
Autoimmune And Inflammatory Diseases ◽  
Biologic Function ◽  
Definite Role ◽  
Inflammatory System

Atherosclerosis is a chronic inflammation characterized by an imbalance between inhibitors and stimulators of the inflammatory system that leads to the formation of atherosclerotic plaques in the vessel walls. Interleukin (IL)-27 is one of the recently discovered cytokines that have an immunomodulatory role in autoimmune and inflammatory diseases. However, the definite role of IL-27 in the pathogenesis of atherosclerosis remains unclear. Recent studies on cardiomyocytes and vascular endothelium have demonstrated mechanisms through which IL-27 could potentially modulate atherosclerosis. Upregulation of the IL-27 receptor was also observed in the atherosclerotic plaques. In addition, circulatory IL-27 levels were increased in patients with acute coronary syndrome and myocardial infarction. A regenerative, neovascularization, and cardioprotective role of IL-27 has also been implicated. Future studies are warranted to elucidate the biologic function and clinical significance of IL-27 in atherosclerosis.

scholarly journals COVID-19 associated cardiac disease: Is there a role of neutrophil extracellular traps in pathogenesis?

2021 ◽  
Vol 8 (4) ◽  
pp. 275-290
Author(s):  
Amal Feiroze Farouk ◽  
◽  
Areez Shafqat ◽  
Shameel Shafqat ◽  
Junaid Kashir ◽  
...  
Keyword(s):  
Cardiac Disease ◽  
Inflammatory Diseases ◽  
Neutrophil Extracellular Traps ◽  
Future Research ◽  
Cardiac Events ◽  
Extracellular Traps ◽  
Adverse Cardiac Events ◽  
New Research ◽  
The Relationship

<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>

scholarly journals Carbohydrate-controlled serine protease inhibitor (serpin) production in Bifidobacterium longum subsp. longum

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
S. Duboux ◽  
M. Golliard ◽  
J. A. Muller ◽  
G. Bergonzelli ◽  
C. J. Bolten ◽  
...  
Keyword(s):  
Protease Inhibitor ◽  
Serine Protease ◽  
Serine Proteases ◽  
Intestinal Tract ◽  
Defense Mechanism ◽  
Inflammatory Diseases ◽  
Bifidobacterium Longum ◽  
Serine Protease Inhibitor ◽  
Innate Defense

AbstractThe Serine Protease Inhibitor (serpin) protein has been suggested to play a key role in the interaction of bifidobacteria with the host. By inhibiting intestinal serine proteases, it might allow bifidobacteria to reside in specific gut niches. In inflammatory diseases where serine proteases contribute to the innate defense mechanism of the host, serpin may dampen the damaging effects of inflammation. In view of the beneficial roles of this protein, it is important to understand how its production is regulated. Here we demonstrate that Bifidobacterium longum NCC 2705 serpin production is tightly regulated by carbohydrates. Galactose and fructose increase the production of this protein while glucose prevents it, suggesting the involvement of catabolite repression. We identified that di- and oligosaccharides containing galactose (GOS) and fructose (FOS) moieties, including the human milk oligosaccharide Lacto-N-tetraose (LNT), are able to activate serpin production. Moreover, we show that the carbohydrate mediated regulation is conserved within B. longum subsp. longum strains but not in other bifidobacterial taxons harboring the serpin coding gene, highlighting that the serpin regulation circuits are not only species- but also subspecies- specific. Our work demonstrates that environmental conditions can modulate expression of an important effector molecule of B. longum, having potential important implications for probiotic manufacturing and supporting the postulated role of serpin in the ability of bifidobacteria to colonize the intestinal tract.

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.

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