Pulmonary epithelial plasma membrane rupture and barrier function disruption during airway reopening.

摘要

Mechanical ventilation inevitably exposes the delicate tissues of the airways and alveoli to a wide range of abnormal stresses that can induce pulmonary edema and initiate or exacerbate life-threatening conditions such as acute lung injury and acute respiratory distress syndrome. The goal of our research is to characterize the cellular trauma caused by the transient, abnormal mechanical stresses that arise when air is forced into a liquidoccluded airway. Using a fluid-filled parallel-plate flow chamber to model this "airway reopening" process, our in vitro study specifically examined consequent increases in pulmonary epithelial plasma membrane rupture, paracellular permeability, and tight junction (TJ) protein disruption. Through this analysis, we observed a distinct, unexpected drop in pulmonary epithelial injury during particularly traumatic reopening events if DeltaPcell -- the reopening-induced fore-aft pressure difference exerted across the cells -- was greater than a critical value, DeltaPcrit. Namely, when DeltaP cell DeltaPcrit, plasma membrane rupture, paracellular permeability and TJ disruption were magnified by increases in DeltaP cell. On the other hand, further enhancing DeltaPcell beyond DeltaP crit consistently and dramatically diminished cell wounding. From these results, we propose that a passive DeltaPcell-induced shift in pulmonary epithelial rheology when DeltaPcell > DeltaP crit prevents excessive cellular trauma during airway reopening which may be exploited to improve patient prognosis during mechanical ventilation.