scholarly journals Mesenchymal stromal cell-derived extracellular vesicles reduce lung inflammation and damage in nonclinical acute lung injury: Implications for COVID-19

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0259732
Author(s):  
Caryn Cloer ◽  
Laila Roudsari ◽  
Lauren Rochelle ◽  
Timothy Petrie ◽  
Michaela Welch ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Extracellular Vesicles ◽  
Immune Modulation ◽  
Therapeutic Potential ◽  
Dose Range ◽  
Surface Protein ◽  
Respiratory Dysfunction ◽  
Cellular Environment ◽  
Alveolar Capillary

Mesenchymal stem cell derived extracellular vesicles (MSC-EVs) are bioactive particles that evoke beneficial responses in recipient cells. We identified a role for MSC-EV in immune modulation and cellular salvage in a model of SARS-CoV-2 induced acute lung injury (ALI) using pulmonary epithelial cells and exposure to cytokines or the SARS-CoV-2 receptor binding domain (RBD). Whereas RBD or cytokine exposure caused a pro-inflammatory cellular environment and injurious signaling, impairing alveolar-capillary barrier function, and inducing cell death, MSC-EVs reduced inflammation and reestablished target cell health. Importantly, MSC-EV treatment increased active ACE2 surface protein compared to RBD injury, identifying a previously unknown role for MSC-EV treatment in COVID-19 signaling and pathogenesis. The beneficial effect of MSC-EV treatment was confirmed in an LPS-induced rat model of ALI wherein MSC-EVs reduced pro-inflammatory cytokine secretion and respiratory dysfunction associated with disease. MSC-EV administration was dose-responsive, demonstrating a large effective dose range for clinical translation. These data provide direct evidence of an MSC-EV-mediated improvement in ALI and contribute new insights into the therapeutic potential of MSC-EVs in COVID-19 or similar pathologies of respiratory distress.

scholarly journals The nanocomposite fullerol reduces oxidative stress, pulmonary injury, and mortality in a rat model of acute lung injury

2021 ◽  
Author(s):  
Rosária Aires ◽  
Ildernandes Vieira-Alves ◽  
Leda Maria Coimbra-Campos ◽  
Marina Ladeira ◽  
Teresa Socarras ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
High Mortality ◽  
Therapeutic Potential ◽  
Ex Vivo ◽  
Mortality Rates ◽  
Kaplan Meier ◽  
Pulmonary Damage

BACKGROUND AND PURPOSE Acute lung injury (ALI) is a critical disorder that has high mortality rates, and pharmacological therapies are so far ineffective. The pathophysiology of ALI involves pulmonary oxidative stress and inflammatory response. Fullerol is a carbon nanocomposite that possesses antioxidant and anti-inflammatory properties. Here, we evaluated the therapeutic potential of fullerol and its mechanisms in a model of paraquat-induced ALI. EXPERIMENTAL APPROACH Rats were divided into ALI (paraquat alone), fullerol (paraquat plus fullerol), and control groups. Survival curves were estimated using the Kaplan-Meier method. The myeloperoxidase assay, ELISA, and hematoxylin and eosin staining were used to determine neutrophils infiltration, cytokines production, and histopathological parameters in lung samples, respectively. The antioxidant effect of fullerol was evaluated in vitro and ex vivo. KEY RESULTS Fullerol (0.01 to 0.3 mg/kg) markedly reduced the severe lung injury and high mortality rates observed in ALI rats. Moreover, fullerol (0.03 mg/kg) inhibited the reactive oxygen species formation and lipid peroxidation seen in lungs from ALI rats, and exhibited a potent concentration-dependent (10 to 10 mg/ml) in vitro antioxidant activity. Importantly, fullerol (0.03 mg/kg) inhibited neutrophils accumulation in bronchoalveolar lavage and lungs, and the increase in pulmonary levels of TNF-α, IL-1β, IL-6, and CINC-1 in ALI rats. CONCLUSIONS AND IMPLICATIONS Fullerol treatment was effective in reducing pulmonary damage and ALI-induced mortality, highlighting its therapeutic potential in an ALI condition. Searching for new pharmacological therapies to treat ALI may be desirable especially in view of the new coronavirus disease 2019 that currently plagues the world.

scholarly journals The assessment of severity of lung injury in sepsis

2004 ◽  
Vol 132 (11-12) ◽  
pp. 404-408
Author(s):  
Ljubica Arsenijevic ◽  
Nada Popovic ◽  
Zvezdana Kojic
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Lung Injury Score ◽  
Pulmonary Dysfunction ◽  
Lethal Outcome ◽  
Injury Score ◽  
Respiratory Dysfunction

Adult respiratory distress syndrome (ARDS) is an acute and severe pulmonary dysfunction. It is clinically characterized by dyspnea and tachypnea, progressive hypoxemia (within 12-48 hours), reduction of pulmonary compliance and diffuse bilateral infiltrates seen on pulmonary radiogram. Etiological factors giving rise to development of the syndrome are numerous. The acute lung injury (AU) is defined as the inflammation syndrome and increased permeability, which is associated with radiological and physiological disorders. Lung injury score (LIS), which is composed of four components, is used for making a distinction between two separate but rather similar syndromes. The study was aimed at the assessment of the severity of the lung injury in patients who had suffered from sepsis of the gynecological origin and its influence on the outcome of the disease. The total of 43 female patients was analyzed. Twenty patients (46.51%) were diagnosed as having ARDS based on the lung injury score, while 23 patients (53.48%) were diagnosed with acute lung injury. In our series, lung injury score ranged from 0.7 to 3.3 in ARDS patients, and lethal outcome ensued in 11 (55%) cases in this group. As for the patients with the acute lung injury, the score values ranged from 0.3 to 1.3 and only one patient from this group died (4.34%). The obtained results indicate that high values of the lung injury score are suggestive of the severe respiratory dysfunction as well as that lethal outcome is dependent on LIS value.

YiQiFuMai Lyophilized Injection Attenuates Sepsis-Induced Acute Lung Injury via TLR4/Src/VE-cadherin/p120-catenin Signaling Pathway

2020 ◽  
Author(s):  
Xue-wei Pan ◽  
Li-xuan Xue ◽  
Qian-liu Zhou ◽  
Jia-zhi Zhang ◽  
Yu-jie Dai ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Signaling Pathway ◽  
Therapeutic Potential ◽  
Cecal Ligation ◽  
Inflammatory Cells ◽  
Underlying Mechanism ◽  
Lavage Fluid ◽  
Lung Edema ◽  
P120 Catenin

Abstract Background: Sepsis is a severe disorder leading to a clinically critical syndrome of multiple organ dysfunction syndrome. Most patients with sepsis will be associated with acute lung injury (ALI), which is an independent risk factors of organ failure and death in patients with sepsis at the same time. YiQiFuMai Lyophilized Injection (YQFM) is a modern traditional Chinese prescription preparation, which could ameliorate ALI induced by lipopolysaccharide (LPS) or fine particulate matter. The current study aimed to investigate the effect of YQFM on sepsis-induced ALI and the underlying mechanism.Methods: Male C57BL/6J mice were treated with cecal ligation and puncture (CLP) after tail intravenous injected with YQFM (1, 2 and 4 g/kg). The measurements of lung edema, evans blue leakage, myeloperoxidase content, inflammatory cells in bronchoalveolar lavage fluid, histopathological assay and expression of associated proteins were performed at 18 h after CLP.Results: The results illustrated that YQFM inhibited pulmonary edema and inflammatory response, thus ameliorated ALI in sepsis mice. Furthermore, the expression of TLR4 and phosphorylated Src was down-regulated, and the expression of p120-catenin and VE-cadherin was restored by YQFM administration.Conclusion: Our study suggested the therapeutic potential of YQFM on treating sepsis-induced ALI via regulating TLR4/Src/VE-cadherin/p120-catenin signaling pathway.

scholarly journals Acute Lung Injury Induced by Staphylococcal enterotoxin B: Disruption of Terminal Vessels as a Mechanism of Induction of Vascular Leak

2012 ◽  
Vol 18 (3) ◽  
pp. 445-452 ◽  
Author(s):  
Ali Imran Saeed ◽  
Sadiye Amcaoglu Rieder ◽  
Robert L. Price ◽  
James Barker ◽  
Prakash Nagarkatti ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Staphylococcal Enterotoxin ◽  
Pulmonary Vasculature ◽  
Tunel Staining ◽  
Staphylococcal Enterotoxin B ◽  
Vascular Leak ◽  
Capillary Membrane ◽  
Enterotoxin B ◽  
Alveolar Capillary

AbstractThe current hypothesis of alveolar capillary membrane dysfunction fails to completely explain the severe and persistent leak of protein-rich fluid into the pulmonary interstitium, seen in the exudative phase of acute lung injury (ALI). The presence of intact red blood cells in the pulmonary interstitium may suggest mechanical failure of pulmonary arterioles and venules. These studies involved the pathological and ultrastructural evaluation of the pulmonary vasculature in Staphylococcal enterotoxin B (SEB)-induced ALI. Administration of SEB resulted in a significant increase in the protein concentration of bronchoalveolar lavage fluid and vascular leak in SEB-exposed mice compared to vehicle-treated mice. In vivo imaging of mice demonstrated the pulmonary edema and leakage in the lungs of SEB-administered mice. The histopathological studies showed intense clustering of inflammatory cells around the alveolar capillaries with subtle changes in architecture. Electron microscopy studies further confirmed the diffuse damage and disruption in the muscularis layer of the terminal vessels. Cell death in the endothelial cells of the terminal vessels was confirmed with TUNEL staining. In this study, we demonstrated that in addition to failure of the alveolar capillary membrane, disruption of the pulmonary arterioles and venules may explain the persistent and severe interstitial and alveolar edema.

scholarly journals Therapeutic Potential of Mesenchymal Stem Cells for Severe Acute Lung Injury

CHEST Journal ◽  
2010 ◽  
Vol 138 (4) ◽  
pp. 965-972 ◽  
Author(s):  
Michael A. Matthay ◽  
B. Taylor Thompson ◽  
Elizabeth J. Read ◽  
David H. McKenna ◽  
Kathleen D. Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Therapeutic Potential

Tyrosol attenuates lipopolysaccharide-induced acute lung injury by inhibiting the inflammatory response and maintaining the alveolar capillary barrier

2017 ◽  
Vol 109 ◽  
pp. 526-533 ◽  
Author(s):  
Yeon-Yong Kim ◽  
Soyoung Lee ◽  
Min-Jong Kim ◽  
Byeong-Cheol Kang ◽  
Hima Dhakal ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Response ◽  
Capillary Barrier ◽  
Alveolar Capillary

scholarly journals Comprehensive Analysis of the Profiles of Differentially Expressed mRNAs, lncRNAs, and circRNAs in Phosgene-Induced Acute Lung Injury

2021 ◽  
Vol 2021 ◽  
pp. 1-22
Author(s):  
Yiru Shao ◽  
Zhifeng Jiang ◽  
Daikun He ◽  
Jie Shen
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Therapeutic Potential ◽  
Expression Profiles ◽  
Mirna Gene ◽  
Differentially Expressed ◽  
Control Group ◽  
Group A ◽  
Group B ◽  
Air Control

Phosgene exposure can cause acute lung injury (ALI), for which there is no currently available effective treatment. Mesenchymal stem cells (MSCs) which have been proven to have therapeutic potential and be helpful in the treatment of various diseases, but the mechanisms underlying the function of MSCs against phosgene-induced ALI are still poorly explored. In this study, we compared the expression profiles of mRNAs, lncRNAs, and circRNAs in the lung tissues from rats of three groups—air control (group A), phosgene-exposed (group B), and phosgene + MSCs (group C). The results showed that 389 mRNAs, 198 lncRNAs, and 56 circRNAs were differently expressed between groups A and B; 130 mRNAs, 107 lncRNAs, and 35 circRNAs between groups A and C; and 41 mRNAs, 88 lncRNAs, and 18 circRNAs between groups B and C. GO and KEGG analyses indicated that the differentially expressed RNAs were mainly involved in signal transduction, immune system processes, and cancers. In addition, we used a database to predict target microRNAs (miRNAs) interacting with circRNAs and the R network software package to construct a circRNA-targeted miRNA gene network map. Our study showed new insights into changes in the RNA expression in ALI, contributing to explore the mechanisms underlying the therapeutic potential of MSCs in phosgene-induced ALI.

scholarly journals Biocompatible N-acetyl-nanoconstruct alleviates lipopolysaccharide-induced acute lung injury in vivo

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Seongchan Kim ◽  
Shin Young Kim ◽  
Seung Joon Rho ◽  
Seung Hoon Kim ◽  
So Hyang Song ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Intratracheal Instillation ◽  
Sprague Dawley ◽  
In Vivo Experiments ◽  
Anti Inflammatory

AbstractOxidative stress plays important roles in inflammatory responses during acute lung injury (ALI). Recently, nanoconstruct (Nano)-based drug-delivery systems have shown promise in many models of inflammation. In this study, we evaluated the anti-inflammatory effects of N-acetylcysteine (NAC) loaded in a biocompatible Nano using a rat model of ALI. We synthesized a Nano with a good NAC-releasing capacity using porous silica Nano, which was used to produce Nano/NAC complexes. For in vivo experiments, Sprague–Dawley rats were intraperitoneally administered NAC or Nano/NAC 30 min after intratracheal instillation of lipopolysaccharide. After 6 h, bronchoalveolar lavage fluids and lung tissues were collected. The anti-oxidative effect of the Nano/NAC complex was confirmed by demonstrating reduced levels of reactive oxygen species after treatment with the Nano/NAC in vitro. In vivo experiments also showed that the Nano/NAC treatment may protect against LPS‐induced ALI thorough anti‐oxidative and anti‐inflammatory effects, which may be attributed to the inactivation of the NF‐κB and MAPK pathways. In addition, the effects of Nano/NAC treatment were shown to be superior to those of NAC alone. We suggest the therapeutic potential of Nano/NAC treatment as an anti‐inflammatory agent against ALI. Furthermore, our study can provide basic data for developing nanotechnology-based pharmacotherapeutics for ALI.

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