LATE-BREAKING ABSTRACT: Interfacial sensing a new regulator of pulmonary epithelial barrier function

Alveolar Type II cells (AT II cells) are located in the alveoli of the lung and are in close proximity to an air-liquid-interface. An important function of AT II cells is the production and secretion of pulmonary surfactant.Pulmonary surfactant is an essential substance, which reduces the high surface tension acting at the alveolar interface. As AT II cells are responsible for the regulation and maintenance of alveolar structures and processes, we suggest that changes of the extracellular environment lead to a fast feedback response via functional and morphological changes in the cells. To test this hypothesis, primary AT II cells were grown on cell culture inserts with porous membranes for longer time periods. We discovered that AT II cells cultured at the immersed-liquid-interface (ILI) show a significantly higher transepithelial electrical resistance (TER) in comparison to cells cultured at air-liquid-interface (ALI). Interestingly, the loss of intercellular tightness was not principally based on changes in tight junction protein expression, but we observed dramatic and quick alterations in actin cytoskeleton formation. The TER effect was not observed when ALI treated cells were covered with a hyperthin layer of surfactant. Therefore, we suggest that the surface tension, which acts on the air exposed cells, induces a fast cell response via phospholipase C activation and calcium influx, which leads to actin reformation followed by functional and morphological cell differentiation. We propose that this newly discovered mechanism of interfacial sensing is essential for the AT II cells for maintaining the sensitive alveolar lining fluid homeostasis during physiological and pathophysiological settings.