scholarly journals Neutrophils as Main Players of Immune Response towards Nondegradable Nanoparticles

Nanomaterials ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 1273 ◽  
Author(s):  
Rostyslav Bilyy ◽  
Galyna Bila ◽  
Oleg Vishchur ◽  
Volodymyr Vovk ◽  
Martin Herrmann
Keyword(s):  
Immune Response ◽  
Bile Ducts ◽  
Soft Tissues ◽  
Neutrophil Extracellular Traps ◽  
Synthetic Polymers ◽  
Surrounding Tissue ◽  
Tubular Structures ◽  
Natural Sources ◽  
Extracellular Traps ◽  
Related Machines

Many nano/microparticles (n/µP), to which our body is exposed, have no physiological way of removal. Our immune system sense these “small particulate objects”, and tries to decrease their harmfulness. Since oxidation, phagocytosis and other methods of degradation do not work with small, chemically resistant, and hydrophobic nanoparticles (nP). This applies to soot from air pollution, nano-diamonds from cosmic impact, polishing and related machines, synthetic polymers, and dietary n/µP. Our body tries to separate these from the surrounding tissue using aggregates from neutrophil extracellular traps (NETs). This effectively works in soft tissues where n/µP are entrapped into granuloma-like structures and isolated. The interactions of hydrophobic nanocrystals with circulating or ductal patrolling neutrophils and the consequent formation of occlusive aggregated NETs (aggNETs) are prone to obstruct capillaries, bile ducts in gallbladder and liver, and many more tubular structures. This may cause serious health problems and often fatality. Here we describe how specific size and surface properties of n/µP can activate neutrophils and lead to aggregation-related pathologies. We discuss “natural” sources of n/µP and those tightly connected to unhealthy diets.

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 Coronavirus disease 2019 (COVID-19): NETosis-associated mechanisms of progression and prospects for therapy regulating the formation of neutrophil extracellular traps (NETs)

2021 ◽  
Vol 6 (4) ◽  
pp. 64-73
Author(s):  
K. A. Aitbaev ◽  
I. T. Murkamilov ◽  
V. V. Fomin ◽  
I. O. Kudaibergenova ◽  
F. A. Yusupov
Keyword(s):  
Molecular Mechanisms ◽  
Adverse Reactions ◽  
Thrombus Formation ◽  
The Elderly ◽  
Neutrophil Extracellular Traps ◽  
The Body ◽  
Surrounding Tissue ◽  
Chronic Respiratory Diseases ◽  
Small Vessels ◽  
Extracellular Traps

Infectious disease COVID-19 caused by the SARS-CoV-2 coronavirus is characterized by high contagiousness, complexity of pathogenesis and unpredictability of the clinical course. In severe cases, which are especially susceptible to men, the elderly and people with underlying medical conditions such as obesity, diabetes, hypertension, cardiovascular and chronic respiratory diseases, the infection leads to respiratory failure and death due to the development of an extensive inflammatory reaction. As a result of many studies, it has been established that one of the leading causes of the severe course and death of patients with COVID-19 is the development of coagulopathy, that is, increased thrombus formation in small vessels due to excessive activity of neutrophils, which form the so-called neutrophil extracellular traps (NETs). Although NETs play a useful role in protecting their host from pathogens, their overgrowth can trigger a cascade of adverse reactions including: the production of antibodies against the host’s DNA (autoimmunization); damage to surrounding tissue; or the occurrence of thromboembolic complications. Therefore, extracellular neutrophil traps and their markers have been identified as targets for new therapeutic strategies aimed at reducing the severity of COVID-19 disease and/or mortality. This article describes the structure of NETs, as well as analyzes the molecular mechanisms that contribute to their overgeneration. In addition, the prospects for COVID-19 therapy aimed at regulating the formation of extracellular traps by creating drugs both limiting the production of NET structures and dissolving their excess amounts in the body of patients are discussed.

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 SARS-CoV2 may evade innate immune response, causing uncontrolled neutrophil extracellular traps formation and multi-organ failure

2020 ◽  
Vol 134 (12) ◽  
pp. 1295-1300 ◽  
Author(s):  
Alain R. Thierry ◽  
Benoit Roch
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Rapid Evolution ◽  
Neutrophil Extracellular Traps ◽  
Innate Immune ◽  
Biological Features ◽  
Extracellular Traps ◽  
Clinical Conditions ◽  
By Products ◽  
New Strategies

Abstract We demonstrate that the general clinical conditions, risk factors and numerous pathological and biological features of COVID-19 are analogous with various disorders caused by the uncontrolled formation of neutrophil extracellular traps and their by-products. Given the rapid evolution of this disease’s symptoms and its lethality, we hypothesize that SARS-CoV2 evades innate immune response causing COVID-19 progresses under just such an amplifier loop, leading to a massive, uncontrolled inflammation process. This work allows us to propose new strategies for treating the pandemic.

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 ROLE OF NEUTROPHIL EXTRACELLULAR TRAPS IN ESPECIALLY DANGEROUS BACTERIAL INFECTIONS

2016 ◽  
pp. 95-104
Author(s):  
A. L. Kravtsov
Keyword(s):  
Experimental Data ◽  
Immune Response ◽  
Bacterial Infections ◽  
Neutrophil Extracellular Traps ◽  
Bactericidal Effect ◽  
Pathogenic Microorganisms ◽  
Extracellular Traps ◽  
Contemporary View ◽  
Causative Agents

Novel data on neutrophil extracellular traps (NET), carrying out capture and killing of pathogenic microorganisms with higher effectiveness than during phagocytosis, are presented. A contemporary view on how neutrophils choose intracellular (phagocytosis) or extracellular (NETosis) mechanism of bactericidity during interaction with pathogenic microorganisms is given. Experimental data on the presence in causative agents of plague, cholera and melioidosis of mechanisms of protection from bactericidal effect of NET, as well as NET’S role in regulation of immune response and sepsis development are analyzed.

scholarly journals Rapid Generation of Coronaviral Immunity Using Recombinant Peptide Modified Nanodiamonds

Pathogens ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 861
Author(s):  
Rostyslav Bilyy ◽  
Quentin Pagneux ◽  
Nathan François ◽  
Galyna Bila ◽  
Roman Grytsko ◽  
...  
Keyword(s):  
Immune Response ◽  
Neutrophil Extracellular Traps ◽  
Fusion Inhibitor ◽  
Recombinant Peptide ◽  
Vaccine Candidates ◽  
Extracellular Traps ◽  
Vaccine Initiation ◽  
Rapid Generation ◽  
Living Organisms ◽  
High Level

Vaccination remains one of the most effective tools to prevent infectious diseases. To ensure that the best possible antigenic components are chosen to stimulate a cognitive immune response, boosting antigen presentation using adjuvants is common practice. Nanodiamond-based adjuvants are proposed here as a rapid and versatile platform for antigen conjugation, utilizing peptides common to different pathogenic strains and making this strategy a good candidate for a “ready-to-use” vaccine. Initiation of an inflammatory reaction with a resulting immune response is based on the ability of living organisms to entrap nanostructures such as nanodiamonds with neutrophil extracellular traps (NETs) formation. In this work, coronavirus peptide homological for MERS-CoV, fusion inhibitor, was conjugated to nanodiamonds and used to induce neutrophilic-driven self-limiting inflammation. The resulting adjuvant was safe and did not induce any tissue damage at the site of injection. Mice immunization resulted in IgG titers of ¼,000 within 28 days. Immunization of rabbits resulted in the formation of a high level of antibodies persistently present for up to 120 days after the first immunization (animal lifespan ~3 years). The peptide used for immunization proved to be reactive with sera of convalescent COVID patients, demonstrating the possibility of developing pancoronaviral vaccine candidates.

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