scholarly journals β2 integrin mediates hantavirus-induced release of neutrophil extracellular traps

2014 ◽  
Vol 211 (7) ◽  
pp. 1485-1497 ◽  
Author(s):  
Martin J. Raftery ◽  
Pritesh Lalwani ◽  
Ellen Krautkrӓmer ◽  
Thorsten Peters ◽  
Karin Scharffetter-Kochanek ◽  
...  
Keyword(s):  
Neutrophil Extracellular Traps ◽  
Lung Damage ◽  
Hantavirus Infection ◽  
Human Pathogens ◽  
Integrin Receptors ◽  
Β2 Integrin ◽  
Extracellular Traps ◽  
Nuclear Antigens ◽  
Complement Receptor 3 ◽  
Underlying Mechanisms

Rodent-borne hantaviruses are emerging human pathogens that cause severe human disease. The underlying mechanisms are not well understood, as hantaviruses replicate in endothelial and epithelial cells without causing any cytopathic effect. We demonstrate that hantaviruses strongly stimulated neutrophils to release neutrophil extracellular traps (NETs). Hantavirus infection induced high systemic levels of circulating NETs in patients and this systemic NET overflow was accompanied by production of autoantibodies to nuclear antigens. Analysis of the responsible mechanism using neutrophils from β2 null mice identified β2 integrin receptors as a master switch for NET induction. Further experiments suggested that β2 integrin receptors such as complement receptor 3 (CR3) and 4 (CR4) may act as novel hantavirus entry receptors. Using adenoviruses, we confirmed that viral interaction with β2 integrin induced strong NET formation. Collectively, β2 integrin–mediated systemic NET overflow is a novel viral mechanism of immunopathology that may be responsible for characteristic aspects of hantavirus-associated disease such as kidney and lung damage.

Neutrophil extracellular traps target senescent vasculature for tissue remodeling in retinopathy

Science ◽  
2020 ◽  
Vol 369 (6506) ◽  
pp. eaay5356
Author(s):  
François Binet ◽  
Gael Cagnone ◽  
Sergio Crespo-Garcia ◽  
Masayuki Hata ◽  
Mathieu Neault ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Diabetic Retinopathy ◽  
Mouse Model ◽  
Vascular Remodeling ◽  
Neutrophil Extracellular Traps ◽  
Developed Countries ◽  
Sterile Inflammation ◽  
Extracellular Traps ◽  
Retinal Blood Vessels ◽  
Underlying Mechanisms

In developed countries, the leading causes of blindness such as diabetic retinopathy are characterized by disorganized vasculature that can become fibrotic. Although many such pathological vessels often naturally regress and spare sight-threatening complications, the underlying mechanisms remain unknown. Here, we used orthogonal approaches in human patients with proliferative diabetic retinopathy and a mouse model of ischemic retinopathies to identify an unconventional role for neutrophils in vascular remodeling during late-stage sterile inflammation. Senescent vasculature released a secretome that attracted neutrophils and triggered the production of neutrophil extracellular traps (NETs). NETs ultimately cleared diseased endothelial cells and remodeled unhealthy vessels. Genetic or pharmacological inhibition of NETosis prevented the regression of senescent vessels and prolonged disease. Thus, clearance of senescent retinal blood vessels leads to reparative vascular remodeling.

scholarly journals Neutrophil extracellular traps infiltrate the lung airway, interstitial, and vascular compartments in severe COVID-19

2020 ◽  
Vol 217 (12) ◽  
Author(s):  
Coraline Radermecker ◽  
Nancy Detrembleur ◽  
Julien Guiot ◽  
Etienne Cavalier ◽  
Monique Henket ◽  
...  
Keyword(s):  
Respiratory Failure ◽  
Neutrophil Extracellular Traps ◽  
Pulmonary Complications ◽  
Lung Damage ◽  
Extracellular Traps

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.

scholarly journals Neutrophil Extracellular Traps in Fatal COVID-19-Associated Lung Injury

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Astrid Obermayer ◽  
Lisa-Maria Jakob ◽  
Jasmin D. Haslbauer ◽  
Matthias S. Matter ◽  
Alexandar Tzankov ◽  
...  
Keyword(s):  
Lung Tissue ◽  
Distress Syndrome ◽  
Clinical Presentation ◽  
Diffuse Alveolar Damage ◽  
Treatment Options ◽  
Neutrophil Extracellular Traps ◽  
Lung Damage ◽  
Morphological Evidence ◽  
Potential Treatment ◽  
Extracellular Traps

An excess formation of neutrophil extracellular traps (NETs), previously shown to be strongly associated with cytokine storm and acute respiratory distress syndrome (ARDS) with prevalent endothelial dysfunction and thrombosis, has been postulated to be a central factor influencing the pathophysiology and clinical presentation of severe COVID-19. A growing number of serological and morphological evidence has added to this assumption, also in regard to potential treatment options. In this study, we used immunohistochemistry and histochemistry to trace NETs and their molecular markers in autopsy lung tissue from seven COVID-19 patients. Quantification of key immunomorphological features enabled comparison with non-COVID-19 diffuse alveolar damage. Our results strengthen and extend recent findings, confirming that NETs are abundantly present in seriously damaged COVID-19 lung tissue, especially in association with microthrombi of the alveolar capillaries. In addition, we provide evidence that low-density neutrophils (LDNs), which are especially prone to NETosis, contribute substantially to COVID-19-associated lung damage in general and vascular blockages in particular.

scholarly journals Antimicrobial Activity of Neutrophils Against Mycobacteria

2021 ◽  
Vol 12 ◽  
Author(s):  
Heather A. Parker ◽  
Lorna Forrester ◽  
Christopher D. Kaldor ◽  
Nina Dickerhof ◽  
Mark B. Hampton
Keyword(s):  
Antimicrobial Activity ◽  
Hypochlorous Acid ◽  
Mycobacterial Infection ◽  
Neutrophil Extracellular Traps ◽  
Resistance Mechanisms ◽  
Host Cells ◽  
Bacterial Clearance ◽  
Human Pathogens ◽  
Extracellular Traps ◽  
Reactive Oxidants

The mycobacterium genus contains a broad range of species, including the human pathogens M. tuberculosis and M. leprae. These bacteria are best known for their residence inside host cells. Neutrophils are frequently observed at sites of mycobacterial infection, but their role in clearance is not well understood. In this review, we discuss how neutrophils attempt to control mycobacterial infections, either through the ingestion of bacteria into intracellular phagosomes, or the release of neutrophil extracellular traps (NETs). Despite their powerful antimicrobial activity, including the production of reactive oxidants such as hypochlorous acid, neutrophils appear ineffective in killing pathogenic mycobacteria. We explore mycobacterial resistance mechanisms, and how thwarting neutrophil action exacerbates disease pathology. A better understanding of how mycobacteria protect themselves from neutrophils will aid the development of novel strategies that facilitate bacterial clearance and limit host tissue damage.

β2 integrin mediates hantavirus-induced release of neutrophil extracellular traps

2014 ◽  
Vol 205 (5) ◽  
pp. 2055OIA105
Author(s):  
Martin J. Raftery ◽  
Pritesh Lalwani ◽  
Ellen Krautkrämer ◽  
Thorsten Peters ◽  
Karin Scharffetter-Kochanek ◽  
...  
Keyword(s):  
Neutrophil Extracellular Traps ◽  
Β2 Integrin ◽  
Extracellular Traps

scholarly journals Neutrophil extracellular traps are present in the airways of ENaC-overexpressing mice with cystic fibrosis-like lung disease

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Samantha L. Tucker ◽  
Demba Sarr ◽  
Balázs Rada
Keyword(s):  
Cystic Fibrosis ◽  
Flow Cytometry ◽  
Bacterial Infections ◽  
Lavage Fluid ◽  
Neutrophil Extracellular Traps ◽  
Lung Damage ◽  
Specific Marker ◽  
Extracellular Traps

Abstract Background Neutrophils are key components of the exacerbated inflammation and tissue damage in cystic fibrosis (CF) airways. Neutrophil extracellular traps (NETs) trap and kill extracellular pathogens. While NETs are abundant in the airways of CF patients and have been hypothesized to contribute to lung damage in CF, the in vivo role of NETs remains controversial, partially due to lack of appropriate animal models. The goal of this study was to detect NETs and to further characterize neutrophil-mediated inflammation in the airways of mice overexpressing the epithelial sodium channel (βENaC-Tg mice on C57BL/6 background) in their lung with CF-like airway disease, in the absence of any apparent bacterial infections. Methods Histology scoring of lung tissues, flow cytometry, multiplex ELISA, immunohistochemistry and immunofluorescence were used to characterize NETs and the airway environment in uninfected, βENaC-Tg mice at 6 and 8 weeks of age, the most chronic time points so far studied in this model. Results Excessive neutrophilic infiltration characterized the lungs of uninfected, βENaC-Tg mice at 6 and 8 weeks of age. The bronchoalveolar lavage fluid (BALF) of βENaC-Tg mice contains increased levels of CF-associated cytokines and chemokines: KC, MIP-1α/β, MCP-1, G-CSF, IL-5, and IL-6. The BALF of βENaC-Tg mice contain MPO-DNA complexes, indicative of the presence of NETs. Immunofluorescence and flow cytometry of BALF neutrophils and lung tissues demonstrated increased histone citrullination, a NET-specific marker, in βENaC-Tg mice. Conclusions NETs are detected in the airways of βENaC-Tg mice, in the absence of bacterial infections. These data demonstrate the usefulness of the βENaC-Tg mouse to serve as a model for studying the role of NETs in chronic CF airway inflammation.

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