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Published on: February 20, 2015
Apoptosis of airway epithelial cells in response to meconium
Alexander Zagariya1, Rama Bhat, Gopal Chari
1Neonatology Laboratories, Department of Pediatrics, Michael Reese Hospital, and Division of Neonatology, University of Illinois at Chicago, 804 S. Wood Street, Chicago, IL 60612, USA. zagariya@uic.edu
Abstract:
Meconium aspiration syndrome (MAS) is common among newborn children but its mechanism is unclear. The syndrome is known to produce a strong inflammatory reaction in the lungs resulting in massive cell death. In this work we studied lung cell death by apoptosis after meconium aspiration in forty two-week-old rabbit pups. Analyzing lung samples by ISEL-DNA end labeling demonstrated the specific spread of apoptotic bodies throughout the lungs. These bodies were shrunken and smaller in size compared to normal cells and many of them were lacking cell membranes. About 70% of all apoptotic bodies were found among the airway epithelium cell eight hours after meconium instillation. In comparison, among lung alveolar cells, only about 20% cells were apoptotic in the same animals. In meconium-treated lungs and A549 cells, a significant increase of angiotensinogen mRNA and Caspase-3 expression were observed. The pretreatment of cells with Caspase-3 inhibitor ZVAD-fmk significantly inhibited meconium-induced lung cell death by apoptosis. These findings demonstrate the apoptotic process in meconium-instilled lungs or A549 cells in culture. Our results show lung airway epithelial and A549 cell apoptosis after meconium instillation. We suggest that studies of lung airway epithelial cell death are essential to understanding the pathophysiology of MAS and may present a key point in future therapeutic applications.
Insights
Meconium aspiration syndrome (MAS) causes lung inflammation and cell death in newborns. This study reveals apoptosis in airway epithelial cells as a key mechanism, suggesting therapeutic targets for MAS.
Area of Science:
- Neonatal Medicine
- Pulmonary Pathology
- Cell Biology
Background:
- Meconium aspiration syndrome (MAS) is a frequent complication in newborns, but its underlying mechanisms, particularly lung cell death, remain incompletely understood.
- MAS is characterized by a significant inflammatory response in the lungs, leading to widespread cell death.
Purpose of the Study:
- To investigate the mechanism of lung cell death, specifically apoptosis, following meconium aspiration in a neonatal rabbit model.
- To identify the specific lung cell types affected by meconium-induced apoptosis and explore potential therapeutic targets.
Main Methods:
- Apoptosis was studied in two-week-old rabbit pups after meconium instillation using In Situ End Labeling (ISEL)-DNA end labeling.
- Lung tissue samples were analyzed for apoptotic bodies, cell morphology, and expression of angiotensinogen mRNA and Caspase-3.
- A549 lung cells in culture were used to confirm findings and test the efficacy of a Caspase-3 inhibitor (ZVAD-fmk).
Main Results:
- Meconium aspiration led to the widespread distribution of apoptotic bodies in the lungs of rabbit pups.
- Airway epithelial cells showed a higher rate of apoptosis (approximately 70%) compared to alveolar cells (approximately 20%) eight hours post-instillation.
- Increased angiotensinogen mRNA and Caspase-3 expression were observed in meconium-treated lungs and A549 cells, with Caspase-3 inhibition reducing cell death.
Conclusions:
- Meconium instillation induces apoptosis in lung airway epithelial cells and A549 cells.
- Apoptosis of lung airway epithelial cells is a critical component in the pathophysiology of MAS.
- Targeting airway epithelial cell apoptosis may offer a novel therapeutic strategy for managing MAS.
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