scholarly journals The mercurial nature of neutrophils: still an enigma in ARDS?

2014 ◽  
Vol 306 (3) ◽  
pp. L217-L230 ◽  
Author(s):  
Andrew E. Williams ◽  
Rachel C. Chambers
Keyword(s):  
Clinical Evidence ◽  
Distress Syndrome ◽  
Host Cells ◽  
Oxygen Species ◽  
Pathogenic Microorganisms ◽  
Extracellular Traps ◽  
Pulmonary Cells ◽  
Life Threatening ◽  
Lung Condition ◽  
Excessive Accumulation

The acute respiratory distress syndrome (ARDS) is a life-threatening lung condition resulting from direct and indirect insults to the lung. It is characterized by disruption of the endothelial-epithelial barrier, alveolar damage, pulmonary edema, and respiratory failure. A key feature of ARDS is the accumulation of neutrophils in the lung microvasculature, interstitium, and alveolar space. Despite a clear association between neutrophil influx into the lung and disease severity, there is some debate as to whether neutrophils directly contribute to disease pathogenesis. The primary function of neutrophils is to provide immediate host defense against pathogenic microorganisms. Neutrophils release numerous antimicrobial factors such as reactive oxygen species, proteinases, and neutrophil extracellular traps. However, these factors are also toxic to host cells and can result in bystander tissue damage. The excessive accumulation of neutrophils in ARDS may therefore contribute to disease progression. Central to neutrophil recruitment is the release of chemokines, including the archetypal neutrophil chemoattractant IL-8, from resident pulmonary cells. However, the chemokine network in the inflamed lung is complex and may involve several other chemokines, including CXCL10, CCL2, and CCL7. This review will therefore focus on the experimental and clinical evidence supporting neutrophils as key players in ARDS and the chemokines involved in recruiting them into the lung.

scholarly journals Role of Neutrophil Extracellular Traps in COVID-19 Progression: An Insight for Effective Treatment

Biomedicines ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 31
Author(s):  
María Amparo Blanch-Ruiz ◽  
Raquel Ortega-Luna ◽  
Guillermo Gómez-García ◽  
Maria Ángeles Martínez-Cuesta ◽  
Ángeles Álvarez
Keyword(s):  
Effective Treatment ◽  
Inflammatory Markers ◽  
Distress Syndrome ◽  
Neutrophil Extracellular Traps ◽  
Multiple Organ ◽  
Oxygen Species ◽  
Albumin Ratio ◽  
Extracellular Traps ◽  
Severity Of The Disease

The coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, has resulted in a pandemic with over 270 million confirmed cases and 5.3 million deaths worldwide. In some cases, the infection leads to acute respiratory distress syndrome (ARDS), which is triggered by a cytokine storm and multiple organ failure. Clinical hematological, biochemical, coagulation, and inflammatory markers, such as interleukins, are associated with COVID-19 disease progression. In this regard, neutrophilia, neutrophil-to-lymphocyte ratio (NLR), and neutrophil-to-albumin ratio (NAR), have emerged as promising biomarkers of disease severity and progression. In the pathophysiology of ARDS, the inflammatory environment induces neutrophil influx and activation in the lungs, promoting the release of cytokines, proteases, reactive oxygen species (ROS), and, eventually, neutrophil extracellular traps (NETs). NETs components, such as DNA, histones, myeloperoxidase, and elastase, may exert cytotoxic activity and alveolar damage. Thus, NETs have also been described as potential biomarkers of COVID-19 prognosis. Several studies have demonstrated that NETs are induced in COVID-19 patients, and that the highest levels of NETs are found in critical ones, therefore highlighting a correlation between NETs and severity of the disease. Knowledge of NETs signaling pathways, and the targeting of points of NETs release, could help to develop an effective treatment for COVID-19, and specifically for severe cases, which would help to manage the pandemic.

Heparin induces neutrophil elastase-dependent vital and lytic NET formation

2019 ◽  
Vol 32 (5) ◽  
pp. 359-368 ◽  
Author(s):  
Patrick M Lelliott ◽  
Masatoshi Momota ◽  
Takayuki Shibahara ◽  
Michelle S J Lee ◽  
Nicholas I Smith ◽  
...  
Keyword(s):  
Neutrophil Elastase ◽  
Biological Effects ◽  
Extracellular Dna ◽  
Low Molecular Weight ◽  
Oxygen Species ◽  
Heparin Induced Thrombocytopenia ◽  
Extracellular Traps ◽  
Dna Strands ◽  
Life Threatening ◽  
Dose Dependent

Abstract Heparin is used extensively as an anticoagulant in a broad range of diseases and procedures; however, its biological effects are not limited to coagulation and remain incompletely understood. Heparin usage can lead to the life-threatening complication known as heparin-induced thrombocytopenia (HIT), caused by the development of antibodies against heparin/PF4 complexes. Here, we demonstrate the ability of heparin to induce neutrophil extracellular traps (NETs). NETs occurred with cell lysis and death, but live neutrophils releasing extracellular DNA strands, known as vital NETs, also occurred abundantly. Formation of NETs was time and dose dependent, and required reactive oxygen species and neutrophil elastase. Other compounds related to heparin such as low molecular weight heparin, fondaparinux and heparan sulfate either failed to induce NETs, or did so to a much lesser extent. Our findings suggest the ability of heparin to directly induce NET formation should be considered in the context of heparin treatment and HIT pathogenesis.

scholarly journals Fast-Onset Diffuse Interstitial Lung Disease in Anti-MDA5 Antibodies-Associated Amyopathic Dermatomyositis

2021 ◽  
Vol 11 (2) ◽  
pp. 235-240
Author(s):  
Houari Aissaoui ◽  
Kinan Drak Alsibai ◽  
Naji Khayath
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Distress Syndrome ◽  
Early Stage ◽  
Immunosuppressive Treatment ◽  
Amyopathic Dermatomyositis ◽  
Pulmonary Manifestations ◽  
Life Threatening ◽  
Adequate Management ◽  
Chest Ct Scan

Anti-MDA5 antibodies-associated amyopathic dermatomyositisis a rare autoimmune disease that involve polyarthritis, cutaneous and pulmonary manifestations. The development of rapidly progressing interstitial lung disease is a life-threatening complication. We report the case of a 45-year-old woman without medical history, who was addressed to the Pulmonary Department for a polyarthritis with dry cough and hypoxemic dyspnea. Initially there was neither cutaneous manifestation nor interstitial lung disease on chest CT scan. After a few days, the patient developed fatal acute respiratory failure with diffuse ground glass opacities. Identification of anti-MDA5 antibodies allowed establishing diagnosis, despite the fact that the first immunological assessment was negative. Corticosteroid bolus of 1 g for three days and immunosuppressive treatment by cyclophosphamide was only initiated at the acute respiratory distress syndrome stage. Given the rapidly unfavorable prognosis of this entity of amyopathic dermatomyositis, the testing for anti-MDA5 antibodies should be recommended in case of progressive pulmonary symptoms associated with joint signs in order to identify this disease at an early stage and to begin rapid and adequate management.

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.

scholarly journals Recent Development on Plant Aldehyde Dehydrogenase Enzymes and Their Functions in Plant Development and Stress Signaling

Genes ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 51
Author(s):  
Adesola J. Tola ◽  
Amal Jaballi ◽  
Hugo Germain ◽  
Tagnon D. Missihoun
Keyword(s):  
Plant Development ◽  
Critical Analysis ◽  
Current Knowledge ◽  
Stress Signaling ◽  
Oxygen Species ◽  
Abiotic And Biotic Stresses ◽  
Aldehyde Dehydrogenases ◽  
Biotic Stresses ◽  
Wide Range ◽  
Excessive Accumulation

Abiotic and biotic stresses induce the formation of reactive oxygen species (ROS), which subsequently causes the excessive accumulation of aldehydes in cells. Stress-derived aldehydes are commonly designated as reactive electrophile species (RES) as a result of the presence of an electrophilic α, β-unsaturated carbonyl group. Aldehyde dehydrogenases (ALDHs) are NAD(P)+-dependent enzymes that metabolize a wide range of endogenous and exogenous aliphatic and aromatic aldehyde molecules by oxidizing them to their corresponding carboxylic acids. The ALDH enzymes are found in nearly all organisms, and plants contain fourteen ALDH protein families. In this review, we performed a critical analysis of the research reports over the last decade on plant ALDHs. Newly discovered roles for these enzymes in metabolism, signaling and development have been highlighted and discussed. We concluded with suggestions for future investigations to exploit the potential of these enzymes in biotechnology and to improve our current knowledge about these enzymes in gene signaling and plant development.

scholarly journals Collective aeromedical evacuations of SARS-CoV-2-related ARDS patients in a military tactical plane: a retrospective descriptive study

2021 ◽  
pp. bmjmilitary-2021-001876
Author(s):  
Thibault Martinez ◽  
K Simon ◽  
L Lely ◽  
C Nguyen Dac ◽  
M Lefevre ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Acute Respiratory Distress Syndrome ◽  
Intensive Care ◽  
Respiratory Distress Syndrome ◽  
Selection Criteria ◽  
Distress Syndrome ◽  
Descriptive Study ◽  
Military Aircraft ◽  
Life Threatening ◽  
The Military

After the appearance of the COVID-19 pandemic in France, MEROPE system was created to transform the military tactical ATLAS A400M aircraft into a flying intensive care unit. Collective aeromedical evacuations (aero-MEDEVAC) of patients suffering from SARS-CoV-2-related acute respiratory distress syndrome was performed from June to December 2020. A total of 22 patients were transported during seven missions. All aero-MEDEVAC was performed in safe conditions for patients and crew. No life-threatening conditions occurred during flight. Biohazard controls were applied according to French guidelines and prevented crew contamination. Thanks to rigorous selection criteria and continuous in-flight medical care, the safe transportation of these patients was possible. To the best of our knowledge, this is the first description of collective aero-MEDEVAC of these kinds of patients using a tactical military aircraft. We here describe the patient’s characteristics and the flight’s challenges.

scholarly journals Herba Artemisiae Capillaris Extract Prevents the Development of Streptozotocin-Induced Diabetic Nephropathy of Rat

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Jianan Geng ◽  
Xiaoyan Yu ◽  
Chunyu Liu ◽  
Chengbo Sun ◽  
Menghuan Guo ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Tissue Transglutaminase ◽  
Blood Lipid ◽  
High Dose ◽  
Oxygen Species ◽  
Promising Candidate ◽  
Ecm Degradation ◽  
Stage Renal Disease ◽  
End Stage ◽  
Excessive Accumulation

Diabetic nephropathy (DN) is a major cause of end-stage renal disease throughout the world; until now there is no specific drug available. In this work, we use herba artemisiae capillaris extract (HACE) to alleviate renal fibrosis characterized by the excessive accumulation of extracellular matrix (ECM) in rats, aiming to investigate the protective effect of the HACE on DN. We found that the intragastric treatment of high-dose HACE could reverse the effect of streptozotocin not only to decrease the level of blood glucose and blood lipid in different degree but also further to improve renal functions. It is worth mentioning that the effect of HACE treatment was comparable to the positive drug benazepril. Moreover, we found that HACE treatment could on one hand inhibit oxidative stress in DN rats through regulating enzymatic activity for scavenging reactive oxygen species and on the other hand increase the ECM degradation through regulating the activity of metalloproteinase-2 (MMP-2) and the expression of tissue transglutaminase (tTG), which explained why HACE treatment inhibited ECM accumulation. On the basis of above experimental results, we conclude that HACE prevents DN development in a streptozotocin-induced DN rat model, and HACE is a promising candidate to cure DN in clinic.

scholarly journals High-Frequency Oscillatory Ventilation Combined with Volume Guarantee in a Neonatal Animal Model of Respiratory Distress Syndrome

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Manuel Sánchez Luna ◽  
Martín Santos González ◽  
Francisco Tendillo Cortijo
Keyword(s):  
Animal Model ◽  
High Frequency ◽  
Distress Syndrome ◽  
Lung Surfactant ◽  
High Frequency Oscillatory Ventilation ◽  
Constant Frequency ◽  
Oscillatory Ventilation ◽  
Before And After ◽  
Lung Condition ◽  
High Frequency Oscillatory

Objective. To assess volume guarantee (VG) ventilation combined with high-frequency oscillatory ventilation (HFOV) strategy on PaCO2regulation in an experimental model of neonatal distress syndrome.Methods. Six 2-day-old piglets weighing  kg were used for this interventional experimental study. Animals were ventilated during physiologic lung conditions and after depletion of lung surfactant by bronchoalveolar lavage (BAL). The effect of HFOV combined with VG on PaCO2was evaluated at different high-frequency expired tidal volume (VThf) at constant frequency () and mean airway pressure (mPaw). Fluctuations of the pressure (ΔPhf) around the mPaw and PaCO2were analyzed before and after lung surfactant depletion.Results. PaCO2levels were inversely proportional to VThf. In the physiological lung condition, an increase in VThf caused a significant decrease in PaCO2and an increase in ΔPhf. After BAL, PaCO2did not change as compared with pre-BAL situation as the VThf remained constant by the ventilator.Conclusions. In this animal model, using HFOV combined with VG, changes in the VThf settings induced significant modifications in PaCO2. After changing the lung condition by depletion of surfactant, PaCO2remained unchanged, as the VThf setting was maintained constant by modifications in the ΔPhf done by the ventilator.

Mediastinal teratoma presenting with respiratory distress and cardiogenic shock in a neonate

2020 ◽  
Vol 30 (5) ◽  
pp. 788-789
Author(s):  
Mila Stajevic ◽  
Ivan Dizdarevic ◽  
Igor Krunic ◽  
Vesna Topic
Keyword(s):  
Respiratory Failure ◽  
Cardiogenic Shock ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Emergency Operation ◽  
Fast Growing ◽  
Mediastinal Teratoma ◽  
Venous Compression ◽  
Life Threatening

Abstract Mediastinal teratomas are uncommon, fast-growing thoracic tumours, which are usually diagnosed in childhood or adolescence. Neonatal forms are the rarest and often present with life-threatening respiratory distress syndrome. In our case, respiratory failure in a neonate was aggravated by severe cardiogenic shock due to aortic and systemic venous compression, extreme heart displacement and rotation, necessitating an emergency operation on the first day of life.

scholarly journals NRF2 Activation Inhibits Both TGF-β1- and IL-13-Mediated Periostin Expression in Fibroblasts: Benefit of Cinnamaldehyde for Antifibrotic Treatment

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Yasutaka Mitamura ◽  
Mika Murai ◽  
Chikage Mitoma ◽  
Masutaka Furue
Keyword(s):  
Dermal Fibroblasts ◽  
Treatment Modalities ◽  
Oxygen Species ◽  
Extracellular Matrix Component ◽  
Fibrotic Disease ◽  
Matrix Component ◽  
Nrf2 Activation ◽  
Life Threatening ◽  
Fibrotic Diseases ◽  
Tgf Β1

Systemic fibrosing or sclerotic disorders are life-threatening, but only very limited treatment modalities are available for them. In recent years, periostin (POSTN), a major extracellular matrix component, was established by several studies as a novel key player in the progression of systemic fibrotic disease. In this research, we revealed the involvement of oxidative stress in the expression of POSTN induced by TGF-β1 and IL-13 in dermal fibroblasts. We found that the antioxidant cinnamaldehyde activated the NRF2/HMOX1 pathway. Cinnamaldehyde also alleviated TGF-β1- and IL-13-mediated production of reactive oxygen species and subsequent POSTN upregulation in dermal fibroblasts. In contrast, NRF2 silencing abolished the cinnamaldehyde-mediated downregulation of POSTN. These results suggest that cinnamaldehyde is a broad inhibitor of POSTN expression covering both TGF-β1 and IL-13 signaling. Cinnamaldehyde may thus be beneficial for the treatment of systemic fibrotic diseases.

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