Proteinase‐activated receptors in lung surfactant secretion in alveolar type II cells

Abstract

The epithelial surface of distal lung is continuously exposed to environmental insults that elicit a potentially injurious response involving influx of neutrophils and release of several proteinases to facilitate host‐defense response. These proteinases can activate cellular response through protease‐activated receptors (PARs). The alveolar epithelial type II (T2) cells are important as they synthesize and secrete various components of lung surfactant, which can influence lung compliance and the innate host‐defense in the lung. In this study, we evaluated if one such proteinase, trypsin, influenced the secretion of lung surfactant in T2 cells. The secretion of lung surfactant with trypsin and phorbol myristate acetate (PMA) was measured in 24 h cultured T2 cells that were labeled with [3H]choline. During incubation for two hours, trypsin increased the secretion of lung surfactant in a concentration‐dependent manner. At 1 μg/ml trypsin, the secretion was ~250% of the basal secretion in comparison to ~300% observed with 100ng/ml PMA. Since trypsin can activate PAR2, we evaluated T2 cells for the presence of this receptor. Western blot analysis of freshly isolated and 24 h cultured cells showed that one major band (~45 kDa protein) reacted with the PAR2 antibody suggesting the presence of PAR2 in T2 cells. These results suggest that T2 cells possibly respond to trypsin through PAR2 to increase lung surfactant secretion and contribute to lung host defense following lung injury and neutrophil‐mediated increase in proteinase enzymes.