Fas/FasL-mediated apoptosis in perinatal murine lungs

1 Program in Fetal Medicine, Departments of 2 Pathology and 4 Pediatrics, Women and Infants Hospital, Providence 02905; and Departments of 3 Pathology and Laboratory Medicine, 5 Pediatrics, and 6 Surgery, Brown Medical School, Providence, Rhode Island 02905 Submitted 1 April 2004 ; accepted in final form 19 May 2004 Postcanalicular lung development is characterized by a time-specific increase in alveolar epithelial type II cell apoptosis. We have previously demonstrated that, in fetal rabbits, developmental type II cell apoptosis coincides with transient upregulation of the cell death regulator Fas ligand (FasL). The aims of this study were 1 ) to determine the spatiotemporal patterns of pulmonary apoptosis and Fas / FasL gene expression in the murine model [embryonic day 17 (E17) through postnatal day 5 (P5)], and 2 ) to investigate the functional involvement of the Fas/FasL system by determining the effect of Fas activation and inhibition on perinatal pulmonary apoptosis. The apoptotic activity of alveolar epithelial type II cells, determined by combined TUNEL labeling and anti-surfactant protein B immunohistochemistry, showed a dramatic increase during the perinatal transition (type II cell apoptotic index