Pulmonary alveolar epithelium protects the lung through apoptosis of T lymphocytes

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1. Expression of Fas/Fas ligand in human acute respiratory distress syndrome (ARDS) and induction of apoptosis in T lymphocyte.We examined expression of Fas/Fas ligand (Fas L) in 27 human ARDS autopsy lungs, and determined if it induced apoptosis in Fas-positive Jurkat T lymphocytes. Fas was detected in all the phases of ARDS lungs, whereas Fas L was expressed on alveolar epithelium in the acute phase of ARDS lungs, which decreased in the hyaline membrane and proliferative phases of ARDS. The sections from ARDS lungs induced apoptosis in Jurkat T lymphocytes, frequency of which was highest in the acute phase of ARDS and decreased in the hyaline membrane and proliferative phases of ARDS. This apoptosis in Jurkat T lymphocytes was almost completely inhibited by pretreatment with NOK-1. These results suggested that expression of Fas L in alveolar epithelium played a role in protecting the lung from injury by inducing apoptosis in pro-inflammatory cells such as lymphocytes.2. Expression of … More Fas/Pas ligand in rat isolated pulmonary alveolar type II cells and induction of apoptosis in T lymphocyte.We examined expression of Fas/Fas L in rat isolated pulmonary alveolar type II cells (type II cells), and investigated if it induced apoptosis in Jurkat T lymphocytes. The effect of pretreatment with cytokines (LPS, TNF-a, IL-1b, IL-8) was also examined. Unstimulated type II cells expressed both Fas/Fas L and their mRNA, which were enhanced by pretreatment with cytokines (LPS<TNF-a<IL-8<IL-1b). Five % of Jurkat cells underwent apoptosis after co-cultured with unstimulated type II cells, and the frequency of apoptosis was significantly increased by pretreatment with cytokines (LPS 8 %, TNF-a 17.5 %, IL-1b 20 %, IL-8 22 %). Pretreatment with NOK-1 inhibited cytokine-induced increase of apoptosis in Jurkat cells by 80 %. These results suggested that cytokine-stimulated type II cells induced apoptosis in Fas-positive Jurkat T lymphocytes, and the Fas/Fas L system was specifically involved in this process. Less