Necrosis Rather Than Apoptosis is the Dominant form of Alveolar Epithelial Cell Death in Lipopolysaccharide-Induced Experimental Acute Respiratory Distress Syndrome Model

Shock ◽  
2020 ◽  
Vol 54 (1) ◽  
pp. 128-139
Author(s):  
Nao Tamada ◽  
Kentaro Tojo ◽  
Takuya Yazawa ◽  
Takahisa Goto
Keyword(s):  
Cell Death ◽  
Acute Respiratory Distress Syndrome ◽  
Epithelial Cell ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Alveolar Epithelial Cell ◽  
Dominant Form ◽  
Alveolar Epithelial ◽  
Epithelial Cell Death

scholarly journals Pseudomonas Aeruginosa Induced Cell Death in Acute Lung Injury and Acute Respiratory Distress Syndrome

2020 ◽  
Vol 21 (15) ◽  
pp. 5356
Author(s):  
Rushikesh Deshpande ◽  
Chunbin Zou
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Cell Death ◽  
Acute Respiratory Distress Syndrome ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Lung Epithelial ◽  
Epithelial Cell Death

Pseudomonas aeruginosa is an important opportunistic pathogen responsible for the cause of acute lung injury and acute respiratory distress syndrome. P. aeruginosa isthe leading species isolated from patients with nosocomial infection and is detected in almost all the patients with long term ventilation in critical care units. P. aeruginosa infection is also the leading cause of deleterious chronic lung infections in patients suffering from cystic fibrosis as well as the major reason for morbidity in people with chronic obstructive pulmonary disease. P. aeruginosa infections are linked to diseases with high mortality rates and are challenging for treatment, for which no effective remedies have been developed. Massive lung epithelial cell death is a hallmark of severe acute lung injury and acute respiratory distress syndrome caused by P. aeruginosa infection. Lung epithelial cell death poses serious challenges to air barrier and structural integrity that may lead to edema, cytokine secretion, inflammatory infiltration, and hypoxia. Here we review different types of cell death caused by P. aeruginosa serving as a starting point for the diseases it is responsible for causing. We also review the different mechanisms of cell death and potential therapeutics in countering the serious challenges presented by this deadly bacterium.

scholarly journals Alveolar CCN1 is associated with mechanical stretch and acute respiratory distress syndrome severity

2020 ◽  
Vol 319 (5) ◽  
pp. L825-L832
Author(s):  
Eric D. Morrell ◽  
Serge Grazioli ◽  
Chi Hung ◽  
Osamu Kajikawa ◽  
Susanna Kosamo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Respiratory Distress Syndrome ◽  
Lung Injury ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Mechanical Stretch ◽  
Mechanically Ventilated ◽  
Alveolar Epithelial ◽  
Protein Levels

The cellular communication network factor 1 (CCN1) is a matricellular protein that can modulate multiple tissue responses, including inflammation and repair. We have previously shown that adenoviral overexpression of Ccn1 is sufficient to cause acute lung injury in mice. We hypothesized that CCN1 is present in the airspaces of lungs during the acute phase of lung injury, and higher concentrations are associated with acute respiratory distress syndrome (ARDS) severity. We tested this hypothesis by measuring 1) CCN1 in bronchoalveolar lavage fluid (BALF) and lung homogenates from mice subjected to ventilation-induced lung injury (VILI), 2) Ccn1 gene expression and protein levels in MLE-12 cells (alveolar epithelial cell line) subjected to mechanical stretch, and 3) CCN1 in BALF from mechanically ventilated humans with and without ARDS. BALF CCN1 concentrations and whole lung CCN1 protein levels were significantly increased in mice with VILI ( n = 6) versus noninjured controls ( n = 6). Ccn1 gene expression and CCN1 protein levels were increased in MLE-12 cells cultured under stretch conditions. Subjects with ARDS ( n = 77) had higher BALF CCN1 levels compared with mechanically ventilated subjects without ARDS ( n = 45) ( P < 0.05). In subjects with ARDS, BALF CCN1 concentrations were associated with higher total protein, sRAGE, and worse [Formula: see text]/[Formula: see text] ratios (all P < 0.05). CCN1 is present in the lungs of mice and humans during the acute inflammatory phase of lung injury, and concentrations are higher in patients with increased markers of severity. Alveolar epithelial cells may be an important source of CCN1 under mechanical stretch conditions.

Protective effect of IL-6 on alveolar epithelial cell death induced by hydrogen peroxide

2005 ◽  
Vol 288 (2) ◽  
pp. L342-L349 ◽  
Author(s):  
Hiroshi Kida ◽  
Mitsuhiro Yoshida ◽  
Shigenori Hoshino ◽  
Koji Inoue ◽  
Yukihiro Yano ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Death ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Alveolar Epithelial Cell ◽  
Alveolar Epithelial Cells ◽  
Lung Fibroblasts ◽  
Alveolar Epithelial ◽  
Epithelial Cell Death

The goal of this study was to examine whether IL-6 could directly protect lung resident cells, especially alveolar epithelial cells, from reactive oxygen species (ROS)-induced cell death. ROS induced IL-6 gene expression in organotypic lung slices of wild-type (WT) mice. ROS also induced IL-6 gene expression in mouse primary lung fibroblasts, dose dependently. The organotypic lung slices of WT were more resistant to ROS-induced DNA fragmentation than those of IL-6-deficient (IL-6−/−) mice. WT resistance against ROS was abrogated by treatment with anti-IL-6 antibody. TdT-mediated dUTP nick end labeling stain and electron microscopy revealed that DNA fragmented cells in the IL-6−/− slice included alveolar epithelial cells and endothelial cells. In vitro studies demonstrated that IL-6 reduced ROS-induced A549 alveolar epithelial cell death. Together, these data suggest that IL-6 played an antioxidant role in the lung by protecting lung resident cells, especially alveolar epithelial cells, from ROS-induced cell death.

PMNS EXACERBATE HYPEROXIC LUNG INJURY VIA AUGMENTED ALVEOLAR EPITHELIAL CELL DEATH.

Shock ◽  
2004 ◽  
Vol 21 ◽  
pp. 27
Author(s):  
L. Mantell ◽  
E. J. Miller ◽  
T. Sakuragi ◽  
J. Romashko ◽  
H. Zhu ◽  
...  
Keyword(s):  
Cell Death ◽  
Epithelial Cell ◽  
Lung Injury ◽  
Alveolar Epithelial Cell ◽  
Alveolar Epithelial ◽  
Hyperoxic Lung Injury ◽  
Epithelial Cell Death

scholarly journals SARS-CoV-2 envelope protein causes acute respiratory distress syndrome (ARDS)-like pathological damages and constitutes an antiviral target

Cell Research ◽  
2021 ◽  
Author(s):  
Bingqing Xia ◽  
Xurui Shen ◽  
Yang He ◽  
Xiaoyan Pan ◽  
Feng-Liang Liu ◽  
...  
Keyword(s):  
Cell Death ◽  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Dominant Negative ◽  
Dominant Negative Mutation ◽  
E Protein

AbstractCytokine storm and multi-organ failure are the main causes of SARS-CoV-2-related death. However, the origin of excessive damages caused by SARS-CoV-2 remains largely unknown. Here we show that the SARS-CoV-2 envelope (2-E) protein alone is able to cause acute respiratory distress syndrome (ARDS)-like damages in vitro and in vivo. 2-E proteins were found to form a type of pH-sensitive cation channels in bilayer lipid membranes. As observed in SARS-CoV-2-infected cells, heterologous expression of 2-E channels induced rapid cell death in various susceptible cell types and robust secretion of cytokines and chemokines in macrophages. Intravenous administration of purified 2-E protein into mice caused ARDS-like pathological damages in lung and spleen. A dominant negative mutation lowering 2-E channel activity attenuated cell death and SARS-CoV-2 production. Newly identified channel inhibitors exhibited potent anti-SARS-CoV-2 activity and excellent cell protective activity in vitro and these activities were positively correlated with inhibition of 2-E channel. Importantly, prophylactic and therapeutic administration of the channel inhibitor effectively reduced both the viral load and secretion of inflammation cytokines in lungs of SARS-CoV-2-infected transgenic mice expressing human angiotensin-converting enzyme 2 (hACE-2). Our study supports that 2-E is a promising drug target against SARS-CoV-2.

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