Abstract
BackgroundIschemia/reperfusion (I/R) injury, involved in primary graft dysfunction following lung transplantation, leads to inactivation of intra-alveolar surfactant which facilitates injury of the blood-air barrier. The alveolar epithelial type II cells (AE2 cells) synthesize, store and secrete surfactant; thus, an intracellular surfactant pool stored in lamellar bodies (Lb) can be distinguished from the intra-alveolar surfactant pool. The aim of this study was to investigate ultrastructural alterations of the intracellular surfactant pool in a model, mimicking transplantation-related procedures including flush perfusion, cold ischemia and reperfusion combined with mechanical ventilation.MethodsUsing design-based stereology at the light and electron microscopic level, number, surface area and mean volume of AE2 cells as well as number, size and total volume of Lb were determined in a group subjected to transplantation-related procedures including both I/R injury and mechanical ventilation (I/R group) and a control group.ResultsAfter I/R injury, the mean number of Lb per AE2 cell was significantly reduced compared to the control group, accompanied by a significant increase in the luminal surface area per AE2 cell in the I/R group. This increase in the luminal surface area correlated with the decrease in surface area of Lb per AE2. The number-weighted mean volume of Lb in the I/R group showed a tendency to increase.ConclusionWe suggest that in this animal model the reduction of the number of Lb per AE2 cell is most likely due to stimulated exocytosis of Lb into the alveolar space. The loss of Lb is partly compensated by an increased size of Lb thus maintaining total volume of Lb per AE2 cell and lung. This mechanism counteracts at least in part the inactivation of the intra-alveolar surfactant.
Highlights
Ischemia/reperfusion (I/R) injury, involved in primary graft dysfunction following lung transplantation, leads to inactivation of intra-alveolar surfactant which facilitates injury of the blood-air barrier
It has been shown that the prophylactic delivery of exogenous surfactant preparations via the trachea has no impact on the amount of the intracellular surfactant pool [39], recent data suggest that alterations of the intracellular surfactant can occur already during the early phase following ischemia/reperfusion injury [27]
In summary, we observed a marked decrease in the number of lamellar bodies (Lb) per cell accompanied by an increase of the luminal surface area of the AE2 cells, which is an indirect sign of a fusion of the limiting membrane with the luminal surface
Summary
Ischemia/reperfusion (I/R) injury, involved in primary graft dysfunction following lung transplantation, leads to inactivation of intra-alveolar surfactant which facilitates injury of the blood-air barrier. An intra-cellular surfactant pool within the AE2 cells can be distinguished from an intra-alveolar surfactant pool [7], and alterations of the AE2 cells due to ischemia/reperfusion injury might be involved in the pathogenesis of primary graft dysfunction following clinical lung transplantation. Experimental data derived from a rat model of ischemia/reperfusion injury supports this notion; the surfactant protein C expression was significantly decreased within the first hours and days following reperfusion and correlated with an impaired oxygenation capacity [27] This emphasizes that AE2 cells and changes of the intracellular surfactant pool are important determinants for pulmonary function in this model. We hypothesized that in this model an increased exocytosis of Lb occurs
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