Abstract
Background: Increased levels of apoptosis have been implied in various non-pulmonary conditions frequently found in Down syndrome (DS). Children with DS are at increased risk for acute lung injury and fetal lung development is disrupted in DS. In both processes, apoptosis plays a key role. Nevertheless, pulmonary apoptosis has not been studied in DS.
Aim: We hypothesized that the amount of apoptotic epithelial cells in fetal lungs of DS is increased compared to controls.
Methods: We compared lung tissue sections from autopsies of 21 fetuses with DS and 12 controls (16-24 weeks gestational age (GA)). Sections were double stained with antibodies against pan-cytokeratin (CK) and activated caspase-3 (C3), markers for epithelium and apoptosis. Per section, 7 random photographs were taken at 200x magnification. Spectral imaging software was used to quantify the mean number of pixels that showed colocalization of CK and C3. All sections were H&E stained to determine the presence of canalicular or saccular morphology.
Results: The mean (SD) percentage of CK-positive pixels was equal between DS and controls (27.2% (4.7) versus 27.1% (6.2), p=0.97). The median percentage (IQR) of CK-positive pixels that showed colocalization of C3 was 0.16% (0.18) in DS compared to 0.27% (0.24) in controls (p=0.45). This was independent of GA. The mean (SD) number of CK-positive pixels increased from 22.5% (5.2) to 30.4% (4.6) with the appearance of saccular morphology in controls but not in DS (p=0.01).
Conclusion: The number of apoptotic epithelial cells in lungs of DS fetuses does not differ from controls. We did find a difference in the development of epithelial structures between DS and controls. This might explain anomalies in alveolar development found at birth in DS.
- © 2011 ERS