Related Experiment Video
Updated: Aug 10, 2026
Visualizing Lung Cellular Adaptations during Combined Ozone and LPS Induced Murine Acute Lung Injury
Published on: March 21, 2021
Transmigration across a lung epithelial monolayer delays apoptosis of polymorphonuclear leukocytes
Maowen Hu1, Edmund J Miller, Xinchun Lin
1Department of Surgery, North Shore University Hospital Long Island Jewish Medical Center, Boas-Marks Research Institute, Manhasset, NY 11030, USA.
Background:
Suppression of polymorphonuclear leukocyte (PMNL) apoptosis may cause or exaggerate acute lung injury that is associated with the acute respiratory distress syndrome. We hypothesized that transepithelial migration would modulate PMNL apoptosis.
Method:
PMNLs that were freshly purified from normal volunteers were allowed to migrate across transwell membranes alone or coated with monolayers of human lung epithelial cells in response to chemoattractants (interleukin-8, formyl-methionylleucylphenylalanine and leukotriene B(4)). We assessed for migration efficiency, apoptosis, and functional activity of the PMNLs. Changes in the expression of genes modulating PMNL apoptosis were examined with messenger RNA and protein analyses.
Results:
Transepithelial migration caused a significant decrease in the percentage of apoptotic PMNLs (interleukin-8; from 31% to 16% at 8 hours; P<.01). This apoptotic delay was sustained to at least 20 hours that was associated with prolongation of PMNL functional activity and independent of chemoattractant-type. Gene and protein expression levels of the antiapoptotic proteins Mcl-1 and 14-3-3 zeta were either augmented or preserved by interleukin-8 treatment alone and after transepithelial migration.
Conclusion:
Our data reveal, for the first time, the important role of transepithelial migration in the modulation of PMNL apoptosis and may provide insights into possible novel targets for the regulation of PMNL apoptosis during lung inflammation and injury.
Insights
Transepithelial migration significantly delays polymorphonuclear leukocyte (PMNL) apoptosis, prolonging their functional activity. This finding offers new therapeutic targets for lung inflammation and acute respiratory distress syndrome.
Area of Science:
- Cell Biology
- Immunology
- Pulmonary Medicine
Background:
- Polymorphonuclear leukocyte (PMNL) apoptosis suppression contributes to acute lung injury and acute respiratory distress syndrome.
- Transepithelial migration is investigated as a potential modulator of PMNL apoptosis.
Purpose of the Study:
- To determine if transepithelial migration influences polymorphonuclear leukocyte (PMNL) apoptosis.
- To explore the impact of migration on PMNL functional activity and gene expression.
Main Methods:
- Freshly purified PMNLs migrated across transwell membranes with or without human lung epithelial cells.
- Chemoattractants (interleukin-8, FMLP, LTB4) were used to stimulate migration.
- Apoptosis, migration efficiency, functional activity, and gene/protein expression were assessed.
Main Results:
- Transepithelial migration significantly reduced PMNL apoptosis (31% to 16% at 8 hours).
- This delay in apoptosis was sustained for at least 20 hours, prolonging PMNL function.
- Gene and protein expression of anti-apoptotic factors (Mcl-1, 14-3-3 zeta) were increased.
Conclusions:
- Transepithelial migration plays a crucial role in modulating PMNL apoptosis.
- Findings suggest novel therapeutic targets for regulating PMNL apoptosis in lung inflammation and injury.
