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1.
Int J Mol Sci ; 22(14)2021 Jul 06.
Article in English | MEDLINE | ID: covidwho-1502438

ABSTRACT

Neutrophils form sticky web-like structures known as neutrophil extracellular traps (NETs) as part of innate immune response. NETs are decondensed extracellular chromatin filaments comprising nuclear and cytoplasmic proteins. NETs have been implicated in many gastrointestinal diseases including colorectal cancer (CRC). However, the regulatory mechanisms of NET formation and potential pharmacological inhibitors in the context of CRC have not been thoroughly discussed. In this review, we intend to highlight roles of NETs in CRC progression and metastasis as well as the potential of targeting NETs during colon cancer therapy.


Subject(s)
Colorectal Neoplasms/immunology , Colorectal Neoplasms/pathology , Extracellular Traps/immunology , Neutrophils/immunology , Neutrophils/pathology , Animals , Disease Progression , Extracellular Traps/physiology , Humans , Neoplasm Metastasis/immunology
2.
Cells ; 10(9)2021 08 26.
Article in English | MEDLINE | ID: covidwho-1458477

ABSTRACT

The enlightenment of the formation of neutrophil extracellular traps (NETs) as a part of the innate immune system shed new insights into the pathologies of various diseases. The initial idea that NETs are a pivotal defense structure was gradually amended due to several deleterious effects in consecutive investigations. NETs formation is now considered a double-edged sword. The harmful effects are not limited to the induction of inflammation by NETs remnants but also include occlusions caused by aggregated NETs (aggNETs). The latter carries the risk of occluding tubular structures like vessels or ducts and appear to be associated with the pathologies of various diseases. In addition to life-threatening vascular clogging, other occlusions include painful stone formation in the biliary system, the kidneys, the prostate, and the appendix. AggNETs are also prone to occlude the ductal system of exocrine glands, as seen in ocular glands, salivary glands, and others. Last, but not least, they also clog the pancreatic ducts in a murine model of neutrophilia. In this regard, elucidating the mechanism of NETs-dependent occlusions is of crucial importance for the development of new therapeutic approaches. Therefore, the purpose of this review is to address the putative mechanisms of NETs-associated occlusions in the pathogenesis of disease, as well as prospective treatment modalities.


Subject(s)
Embolism/immunology , Extracellular Traps/physiology , Thrombosis/immunology , Animals , Body Fluids/immunology , Body Fluids/physiology , Embolism/physiopathology , Extracellular Traps/immunology , Extracellular Traps/metabolism , Humans , Inflammation/pathology , Neutrophils/immunology , Prospective Studies , Thrombosis/physiopathology
3.
Cardiovasc Res ; 117(8): 1814-1822, 2021 07 07.
Article in English | MEDLINE | ID: covidwho-1301347

ABSTRACT

2020 has been an extraordinary year. The emergence of COVID-19 has driven urgent research in pulmonary and cardiovascular science and other fields. It has also shaped the way that we work with many experimental laboratories shutting down for several months, while bioinformatics approaches and other large data projects have gained prominence. Despite these setbacks, vascular biology research is stronger than ever. On behalf of the European Society of Cardiology Council for Basic Cardiovascular Science (ESC CBCS), here we review some of the vascular biology research highlights for 2020. This review is not exhaustive and there are many outstanding vascular biology publications that we were unable to cite due to page limits. Notwithstanding this, we have provided a snapshot of vascular biology research excellence in 2020 and identify topics that are in the ascendency and likely to gain prominence in coming years.


Subject(s)
COVID-19/diagnosis , Extracellular Traps/physiology , Neutrophils/cytology , Smartphone , Computational Biology , Humans , SARS-CoV-2/pathogenicity
4.
Cells ; 10(6)2021 06 11.
Article in English | MEDLINE | ID: covidwho-1270009

ABSTRACT

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.


Subject(s)
Extracellular Traps/physiology , Mucous Membrane/immunology , Skin Diseases/immunology , Epithelial Cells/immunology , Host-Pathogen Interactions/immunology , Humans , Immunity, Innate/physiology , Neutrophils/immunology , Neutrophils/physiology , Skin Diseases/pathology
5.
Transl Res ; 232: 13-36, 2021 06.
Article in English | MEDLINE | ID: covidwho-989350

ABSTRACT

As the world navigates the coronavirus disease 2019 (COVID-19) pandemic, there is a growing need to assess its impact in patients with autoimmune rheumatic diseases, such as systemic lupus erythematosus (SLE). Patients with SLE are a unique population when considering the risk of contracting COVID-19 and infection outcomes. The use of systemic glucocorticoids and immunosuppressants, and underlying organ damage from SLE are potential susceptibility factors. Most patients with SLE have evidence of high type I interferon activity, which may theoretically act as an antiviral line of defense or contribute to the development of a deleterious hyperinflammatory response in COVID-19. Other immunopathogenic mechanisms of SLE may overlap with those described in COVID-19, thus, studies in SLE could provide some insight into immune responses occurring in severe cases of the viral infection. We reviewed the literature to date on COVID-19 in patients with SLE and provide an in-depth review of current research in the area, including immune pathway activation, epidemiology, clinical features, outcomes, and the psychosocial impact of the pandemic in those with autoimmune disease.


Subject(s)
COVID-19/etiology , Lupus Erythematosus, Systemic/complications , SARS-CoV-2 , Antibodies, Antiphospholipid/immunology , COVID-19/epidemiology , COVID-19/immunology , Complement System Proteins/physiology , Extracellular Traps/physiology , Health Services Accessibility , Humans , Interferon Type I/physiology , Lupus Erythematosus, Systemic/immunology , TOR Serine-Threonine Kinases/physiology
6.
J Exp Med ; 217(12)2020 12 07.
Article in English | MEDLINE | ID: covidwho-759876

ABSTRACT

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.


Subject(s)
Betacoronavirus/physiology , Coronavirus Infections/immunology , Coronavirus Infections/virology , Extracellular Traps/physiology , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , A549 Cells , Adult , Angiotensin-Converting Enzyme 2 , COVID-19 , Cell Death , Coronavirus Infections/blood , Coronavirus Infections/pathology , Epithelial Cells/pathology , Epithelial Cells/virology , Female , HeLa Cells , Humans , Male , Neutrophil Activation , Pandemics , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/blood , Pneumonia, Viral/pathology , SARS-CoV-2 , Serine Proteases/metabolism , Suction , Trachea/immunology
7.
J Exp Med ; 217(12)2020 12 07.
Article in English | MEDLINE | ID: covidwho-759875

ABSTRACT

Infection with SARS-CoV-2 is causing a deadly and pandemic disease called coronavirus disease-19 (COVID-19). While SARS-CoV-2-triggered hyperinflammatory tissue-damaging and immunothrombotic responses are thought to be major causes of respiratory failure and death, how they relate to lung immunopathological changes remains unclear. Neutrophil extracellular traps (NETs) can contribute to inflammation-associated lung damage, thrombosis, and fibrosis. However, whether NETs infiltrate particular compartments in severe COVID-19 lungs remains to be clarified. Here we analyzed postmortem lung specimens from four patients who succumbed to COVID-19 and four patients who died from a COVID-19-unrelated cause. We report the presence of NETs in the lungs of each COVID-19 patient. NETs were found in the airway compartment and neutrophil-rich inflammatory areas of the interstitium, while NET-prone primed neutrophils were present in arteriolar microthrombi. Our results support the hypothesis that NETs may represent drivers of severe pulmonary complications of COVID-19 and suggest that NET-targeting approaches could be considered for the treatment of uncontrolled tissue-damaging and thrombotic responses in COVID-19.


Subject(s)
Betacoronavirus/physiology , Coronavirus Infections/immunology , Coronavirus Infections/virology , Extracellular Traps/physiology , Lung/blood supply , Lung/virology , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , Aged , COVID-19 , Coronavirus Infections/pathology , Female , Humans , Lung/pathology , Male , Middle Aged , Pandemics , Pneumonia, Viral/pathology , SARS-CoV-2
8.
J Perinat Med ; 48(9): 985-994, 2020 Nov 26.
Article in English | MEDLINE | ID: covidwho-692325

ABSTRACT

An issue of the novel coronavirus infection spreading is currently in the first place among others in the list of the international medical community. Due to lack of information, conflicting research findings, multicomponent effect of the virus on the body host, as well as various consequences that the virus triggers in the body, now every medical specialty does study the viral attack pathogenesis. Recent months showed that vascular complications are the most severe in the Coronavirus Disease 2019 (COVID-19) and are the main cause of death in the patients. The mechanisms of vascular complications are complex and affect both the hemostatic system and immune responses, "inflammatory storm", disorders of the renin-angiotensin-aldosterone system, endotheliopathy, etc. Due to the leading role of vascular complications in the viral infection pathogenesis, several groups of patients are at extra risk, including pregnant women, patients with a burdened obstetric history, with hereditary thrombophilia and antiphospholipid syndrome, and patients after in vitro fertilization (IVF). In this category of pregnant women, use of low-molecular-weight heparins (LMWH) is particularly important for both prevention of vascular and obstetric complications, and for pathogenetic therapy of COVID-19.


Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Extracellular Traps/physiology , Neutrophils/ultrastructure , Pneumonia, Viral/complications , Pregnancy Complications, Infectious/virology , Vascular Diseases/virology , Angiotensin-Converting Enzyme 2 , COVID-19 , Comorbidity , Coronavirus Infections/drug therapy , Coronavirus Infections/epidemiology , Delivery, Obstetric/methods , Female , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Lung/virology , Pandemics , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/drug therapy , Pneumonia, Viral/epidemiology , Pregnancy , Pregnancy Complications, Infectious/drug therapy , Pregnancy Complications, Infectious/physiopathology , Risk Factors , SARS-CoV-2 , Vascular Diseases/epidemiology , Vascular Diseases/prevention & control
9.
Clin Sci (Lond) ; 134(12): 1295-1300, 2020 06 26.
Article in English | MEDLINE | ID: covidwho-599624

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.


Subject(s)
Betacoronavirus/physiology , Coronavirus Infections/immunology , Extracellular Traps/physiology , Host-Pathogen Interactions/immunology , Pneumonia, Viral/immunology , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/drug therapy , Deoxyribonuclease I/therapeutic use , Humans , Immunity, Innate , Multiple Organ Failure/immunology , Multiple Organ Failure/virology , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/drug therapy , SARS-CoV-2
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