scholarly journals Dexmedetomidine Attenuates Bilirubin-Induced Lung Alveolar Epithelial Cell Death In Vitro and In Vivo*

2015 ◽  
Vol 43 (9) ◽  
pp. e356-e368 ◽  
Author(s):  
Jian Cui ◽  
Hailin Zhao ◽  
Bin Yi ◽  
Jing Zeng ◽  
Kaizhi Lu ◽  
...  
Keyword(s):  
Cell Death ◽  
Epithelial Cell ◽  
Alveolar Epithelial Cell ◽  
Alveolar Epithelial ◽  
Epithelial Cell Death

Alveolar epithelial cell death adjacent to underlying myofibroblasts in advanced fibrotic human lung

1998 ◽  
Vol 275 (6) ◽  
pp. L1192-L1199 ◽  
Author(s):  
Bruce D. Uhal ◽  
Iravati Joshi ◽  
W. Frank Hughes ◽  
Carlos Ramos ◽  
Annie Pardo ◽  
...  
Keyword(s):  
Cell Death ◽  
Epithelial Cell ◽  
Human Lung ◽  
Alveolar Epithelial Cell ◽  
Cell Loss ◽  
Alveolar Epithelial ◽  
Picrosirius Red ◽  
Epithelial Cell Death

Earlier work from this laboratory showed that abnormal fibroblast phenotypes isolated from fibrotic human lung produce factor(s) capable of inducing apoptosis and necrosis of alveolar epithelial cells in vitro [B. D. Uhal, I. Joshi, A. True, S. Mundle, A. Raza, A. Pardo, and M. Selman. Am. J. Physiol. 269 ( Lung Cell. Mol. Physiol. 13): L819–L828, 1995]. To determine whether epithelial cell death is associated with proximity to abnormal fibroblasts in vivo, the spatial distribution of epithelial cell loss, DNA fragmentation, and myofibroblasts was examined in the same tissue specimens used previously for fibroblast isolation. Paraffin sections of normal and fibrotic human lung were subjected to in situ end labeling (ISEL) of fragmented DNA and simultaneous immunolabeling of α-smooth muscle actin (α-SMA); replicate samples were subjected to electron microscopy and detection of collagens by the picrosirius red technique. Normal human lung exhibited very little labeling except for positive α-SMA immunoreactivity of smooth muscle surrounding bronchi and vessels. In contrast, fibrotic human lung exhibited moderate to heavy ISEL of interstitial, cuboidal epithelial, and free alveolar cells. ISEL of the alveolar epithelium was not distributed uniformly but was most intense immediately adjacent to underlying foci of α-SMA-positive fibroblast-like interstitial cells. Both electron microscopy and picrosirius red confirmed epithelial cell apoptosis, necrosis, and cell loss adjacent to foci of collagen accumulation surrounding fibroblast-like cells. These results demonstrate that the cuboidal epithelium of the fibrotic lung contains dying as well as proliferating cells and support the hypothesis that alveolar epithelial cell death is induced by abnormal lung fibroblasts in vivo as it is in vitro.

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.

scholarly journals Pneumocystis Pneumonia Increases the Susceptibility of Mice to Sublethal Hyperoxia

2003 ◽  
Vol 71 (10) ◽  
pp. 5970-5978 ◽  
Author(s):  
James M. Beck ◽  
Angela M. Preston ◽  
Steven E. Wilcoxen ◽  
Susan B. Morris ◽  
Eric S. White ◽  
...  
Keyword(s):  
T Cells ◽  
Epithelial Cell ◽  
Cell Injury ◽  
Alveolar Epithelial Cell ◽  
Pulmonary Inflammation ◽  
Alveolar Epithelial Cells ◽  
Alveolar Epithelial ◽  
Epithelial Cell Injury

ABSTRACT Patients with Pneumocystis pneumonia often develop respiratory failure after entry into medical care, and one mechanism for this deterioration may be increased alveolar epithelial cell injury. In vitro, we previously demonstrated that Pneumocystis is not cytotoxic for alveolar epithelial cells. In vivo, however, infection with Pneumocystis could increase susceptibility to injury by stressors that, alone, would be sublethal. We examined transient exposure to hyperoxia as a prototypical stress that does cause mortality in normal mice. Mice were depleted of CD4+ T cells and inoculated intratracheally with Pneumocystis. Control mice were depleted of CD4+ T cells but did not receive Pneumocystis. After 4 weeks, mice were maintained in normoxia, were exposed to hyperoxia for 4 days, or were exposed to hyperoxia for 4 days followed by return to normoxia. CD4-depleted mice with Pneumocystis pneumonia demonstrated significant mortality after transient exposure to hyperoxia, while all uninfected control mice survived this stress. We determined that organism burdens were not different. However, infected mice exposed to hyperoxia and then returned to normoxia demonstrated significant increases in inflammatory cell accumulation and lung cell apoptosis. We conclude that Pneumocystis pneumonia leads to increased mortality following a normally sublethal hyperoxic insult, accompanied by alveolar epithelial cell injury and increased pulmonary inflammation.

scholarly journals Autophagy Decreases Alveolar Epithelial Cell Injury by Suppressing the NF-κB Signaling Pathway and Regulating the Release of Inflammatory Mediators

2018 ◽  
Author(s):  
Tao Fan ◽  
Shuo Yang ◽  
Zhixin Huang ◽  
Wei Wang ◽  
Shize Pan ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Alveolar Epithelial Cell ◽  
Ischemia Reperfusion ◽  
Left Lung ◽  
Alveolar Epithelial ◽  
Group Blocking

AbstractTo research the impact of autophagy on alveolar epithelial cell inflammation and its possible mechanism in early stages of hypoxia, we established a cell hypoxia-reoxygenation model and orthotopic left lung ischemia-reperfusion model. Rat alveolar epithelial cells stably expressing GFP-LC3 were treated with an autophagy inhibitor (3-methyladenine, 3-MA) or autophagy promoter (rapamycin), followed by hypoxia-reoxygenation treatment at 2, 4 and 6h in vitro. In vivo, twenty-four male Sprague-Dawley rats were randomly divided into four groups (model group: no blocking of hilum in the left lung; control group: blocking of hilum in the left lung for 1h with DMSO lavage; 3-MA group: blocking of hilum in the left lung for 1h with 100ml/kg of 3-MA (5μmol/L) solution lavage; rapamycin group: blocking of hilum in the left lung for 1h with 100ml/kg of rapamycin (250nmol/L) solution lavage) to establish an orthotopic left lung ischemia model. This study demonstrated that rapamycin significantly suppressed the NF-κB signaling pathway, restrained the expression of pro-inflammatory factors. A contrary result was confirmed by 3-MA pretreatment. These findings indicate that autophagy reduces ischemia-reperfusion injury by repressing inflammatory signaling pathways in the early stage of hypoxia in vitro and in vivo. This could be a new protective method for lung ischemia-reperfusion injury.

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 Platelets inhibit apoptotic lung epithelial cell death and protect mice against infection-induced lung injury

2019 ◽  
Vol 3 (3) ◽  
pp. 432-445 ◽  
Author(s):  
William Bain ◽  
Tolani Olonisakin ◽  
Minting Yu ◽  
Yanyan Qu ◽  
Mei Hulver ◽  
...  
Keyword(s):  
Cell Death ◽  
Epithelial Cell ◽  
Lung Injury ◽  
Lung Epithelial Cell ◽  
Barrier Disruption ◽  
Lung Epithelial ◽  
Epithelial Cell Death ◽  
Alveolar Capillary

Abstract Thrombocytopenia is associated with worse outcomes in patients with acute respiratory distress syndrome, which is most commonly caused by infection and marked by alveolar–capillary barrier disruption. However, the mechanisms by which platelets protect the lung alveolar–capillary barrier during infectious injury remain unclear. We found that natively thrombocytopenic Mpl−/− mice deficient in the thrombopoietin receptor sustain severe lung injury marked by alveolar barrier disruption and hemorrhagic pneumonia with early mortality following acute intrapulmonary Pseudomonas aeruginosa (PA) infection; barrier disruption was attenuated by platelet reconstitution. Although PA infection was associated with a brisk neutrophil influx, depletion of airspace neutrophils failed to substantially mitigate PA-triggered alveolar barrier disruption in Mpl−/− mice. Rather, PA cell-free supernatant was sufficient to induce lung epithelial cell apoptosis in vitro and in vivo and alveolar barrier disruption in both platelet-depleted mice and Mpl−/− mice in vivo. Cell-free supernatant from PA with genetic deletion of the type 2 secretion system, but not the type 3 secretion system, mitigated lung epithelial cell death in vitro and lung injury in Mpl−/− mice. Moreover, platelet releasates reduced poly (ADP ribose) polymerase cleavage and lung injury in Mpl−/− mice, and boiling of platelet releasates, but not apyrase treatment, abrogated PA supernatant–induced lung epithelial cell cytotoxicity in vitro. These findings indicate that while neutrophil airspace influx does not potentiate infectious lung injury in the thrombocytopenic host, platelets and their factors protect against severe pulmonary complications from pathogen-secreted virulence factors that promote host cell death even in the absence of overt infection.

scholarly journals Extracellular vesicle-cargo miR-185-5p reflects type II alveolar cell death after oxidative stress

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Jonathan M. Carnino ◽  
Heedoo Lee ◽  
Xue He ◽  
Michael Groot ◽  
Yang Jin
Keyword(s):  
Cell Death ◽  
Epithelial Cell ◽  
Alveolar Epithelial Cell ◽  
Extracellular Vesicle ◽  
Alveolar Type ◽  
Type I ◽  
Type Ii ◽  
Alveolar Cells ◽  
Epithelial Cell Death

Abstract Acute respiratory distress syndrome (ARDS) is a devastating syndrome responsible for significant morbidity and mortality. Diffuse alveolar epithelial cell death, including but not limited to apoptosis and necroptosis, is one of the hallmarks of ARDS. Currently, no detectable markers can reflect this feature of ARDS. Hyperoxia-induced lung injury is a well-established murine model that mimics human ARDS. We found that hyperoxia and its derivative, reactive oxygen species (ROS), upregulate miR-185-5p, but not miR-185-3p, in alveolar cells. This observation is particularly more significant in alveolar type II (ATII) than alveolar type I (ATI) cells. Functionally, miR-185-5p promotes expression and activation of both receptor-interacting kinase I (RIPK1) and receptor-interacting kinase III (RIPK3), leading to phosphorylation of mixed lineage kinase domain-like (MLKL) and necroptosis. MiR-185-5p regulates this process probably via suppressing FADD and caspase-8 which are both necroptosis inhibitors. Furthermore, miR-185-5p also promotes intrinsic apoptosis, reflected by enhancing caspase-3/7 and 9 activity. Importantly, extracellular vesicle (EV)-containing miR-185-5p, but not free miR-185-5p, is detectable and significantly elevated after hyperoxia-induced cell death, both in vitro and in vivo. Collectively, hyperoxia-induced miR-185-5p regulates both necroptosis and apoptosis in ATII cells. The extracellular level of EV-cargo miR-185-5p is elevated in the setting of profound epithelial cell death.

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