Alveolar Type 2 Epithelial Cells as Potential Therapeutics for Acute Lung Injury/Acute Respiratory Distress Syndrome

2020 ◽  
Vol 25 (46) ◽  
pp. 4877-4882 ◽  
Author(s):  
Honglei Zhang ◽  
Yong Cui ◽  
Zhiyu Zhou ◽  
Yan Ding ◽  
Hongguang Nie

: Acute lung injury/acute respiratory distress syndrome is a common clinical illness with high morbidity and mortality, which is still one of the medical problems urgently needed to be solved. Alveolar type 2 epithelial cells are an important component of lung epithelial cells and as a kind of stem cells, they can proliferate and differentiate into alveolar type 1 epithelial cells, thus contributing to lung epithelial repairment. In addition, they synthesize and secrete all components of the surfactant that regulates alveolar surface tension in the lungs. Moreover, alveolar type 2 epithelial cells play an active role in enhancing alveolar fluid clearance and reducing lung inflammation. In recent years, as more advanced approaches appear in the field of stem and progenitor cells in the lung, many preclinical studies have shown that the cell therapy of alveolar type 2 epithelial cells has great potential effects for acute lung injury/acute respiratory distress syndrome. We reviewed the recent progress on the mechanisms of alveolar type 2 epithelial cells involved in the damaged lung repairment, aiming to explore the possible therapeutic targets in acute lung injury/acute respiratory distress syndrome.

2020 ◽  
Author(s):  
Hyunwook Lee ◽  
Qinqin Fei ◽  
Adam Streicher ◽  
Wenjuan Zhang ◽  
Colleen Isabelle ◽  
...  

AbstractAcute respiratory distress syndrome (ARDS) is a highly lethal condition that impairs lung function and causes respiratory failure. Mechanical ventilation maintains gas exchange in patients with ARDS, but exposes lung cells to physical forces that exacerbate lung injury. Our data demonstrate that mTOR complex 1 (mTORC1) is a mechanosensor in lung epithelial cells and that activation of this pathway during mechanical ventilation exacerbates lung injury. We found that mTORC1 is activated in lung epithelial cells following volutrauma and atelectrauma in mice and humanized in vitro models of the lung microenvironment. mTORC1 is also activated in lung tissue of mechanically ventilated patients with ARDS. Deletion of Tsc2, a negative regulator of mTORC1, in epithelial cells exacerbates physiologic lung dysfunction during mechanical ventilation. Conversely, treatment with rapamycin at the time mechanical ventilation is initiated prevents physiologic lung injury (i.e. decreased compliance) without altering lung inflammation or barrier permeability. mTORC1 inhibition mitigates physiologic lung injury by preventing surfactant dysfunction during mechanical ventilation. Our data demonstrate that in contrast to canonical mTORC1 activation under favorable growth conditions, activation of mTORC1 during mechanical ventilation exacerbates lung injury and inhibition of this pathway may be a novel therapeutic target to mitigate ventilator induced lung injury during ARDS.


2020 ◽  
Vol 21 (15) ◽  
pp. 5356
Author(s):  
Rushikesh Deshpande ◽  
Chunbin Zou

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.


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