Fig. 2: Loss of TRAIL aggravates hyperoxia-induced alveolar simplification in newborn mice.

A Haematoxylin/eosin staining of representative lung tissue sections from newborn wildtype and TRAIL^−/− mice exposed to 21%, 40% or 85% of oxygen for 7 days starting after birth. Hyperoxia induced alveolar simplification was visible at 40% and 85% of oxygen. Scale bar: 200 µm. B Enlarged image sections from haematoxylin/eosin stainings as in A. Scale bar: 200 µm. C Corresponding lung morphometric analyses for airspace (left panel), mean linear intercept (middle) and septal wall thickness (right panel) from A. Hyperoxia-induced increase in airspace was significantly more pronounced in TRAIL^−/− compared to wildtype mice for 40% and 85% of oxygen. For mean linear intercept, statistical significance was reached at 85% of oxygen. D Mice from A were allowed to recover for another 21 days in room air after exposure to hyperoxic injury before histologic evaluation. Hyperoxia-induced alveolar simplification persisted for 40% and 85% of oxygen. Scale bar: 200 µm. E Enlarged image sections from haematoxylin/eosin stainings as in D. Scale bar: 200 µm. F Lung morphometric analyses for airspace (left panel), mean linear intercept (middle) and septal wall thickness (right panel) were executed for haematoxylin/eosin stainings from D. The statistically significant increase in airspace and mean linear intercept after hyperoxic injury in TRAIL^−/− compared to wildtype mice persisted for 85% of oxygen after the recovery period of 21 days in room air. G Immunofluorescence staining for surfactant protein C (SPC) positive cells of lung tissues from mice from A. Hyperoxia-induced rarefication of SPC cells was detectable at 40% and 85% of oxygen. H Quantification of SPC positive cells from G. Hyperoxia-induced rarefication of SPC positive cells was significantly more pronounced in TRAIL^−/− compared to wildtype mice for 85% of oxygen. I Immunofluorescence staining for platelet derived growth factor receptor α (PDGFRα) positive cells of lung tissues from mice from A. Hyperoxia-induced rarefication of PDGFRα cells was visible at 40% and 85% of oxygen. J Quantification of PDGFRα positive cells from I. Hyperoxia-induced rarefication of PDGFRα positive cells was significantly more pronounced in TRAIL^−/− compared to wildtype mice for 85% of oxygen. K Immunofluorescence staining for vascular endothelial CD31 positive cells of lung tissues from mice from A. Hyperoxia-induced rarefication of CD31 cells was apparent at 40% and 85% of oxygen. L Quantification of CD31 positive cells from K. Hyperoxia-induced rarefication of CD31 positive cells was significantly more pronounced in TRAIL^−/− compared to wildtype mice for 85% of oxygen. Data are presented as mean + SEM. Statistical analysis was performed by t-test. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. n ≥ 6 mice/group.