title: Pulmonary epithelial apoptosis in fetal down syndrome: not higher than normal.
abstract: Children with Down syndrome (DS) are at high risk for acute lung injury (ALI). Pulmonary epithelial apoptosis is an important factor in the pathophysiology of ALI. Whether the risk of ALI in DS is associated with a high level of pulmonary epithelial apoptosis is not known. We hypothesized that the percentage of apoptotic epithelial cells is higher in DS than in control lungs. Lung tissue sections from autopsies of 21 fetuses with DS and 12 controls were stained with antibodies against the epithelial marker pan-cytokeratin (CK) and apoptosis marker activated caspase-3 (aC3). Spectral imaging software was used to quantify the mean percentage of pixels that showed colocalization of CK and aC3. Mean (standard deviation [SD]) gestational age in weeks was 18.7 (1.4) in DS and 18.9 (2.0) in controls (P  =  0.67). The mean (SD) percentage of CK-positive pixels was 27.2% (4.7%) in DS compared to 27.1% (6.2%) in controls (P  =  0.97). The median (interquartile range [IQR]) percentage of CK-positive pixels that showed colocalization of aC3 was 0.16% (0.18%) in DS compared to 0.27% (0.24%) in controls (P  =  0.45). 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). The percentage of apoptotic epithelial cells in DS fetal lungs does not differ from that in controls. However, we did find a difference in the development of epithelial structures between DS and controls that may be associated with anomalies in alveolar development found at birth in DS.
authors.affiliation: Emma Children's Hospital/Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. m.bruijn@amc.nl
authors.forename: Martijn
authors.initials: M
authors.lastname: Bruijn
authors.forename: Jan H
authors.initials: JH
authors.lastname: von der Thüsen
authors.forename: Chris M
authors.initials: CM
authors.lastname: van der Loos
authors.forename: Ronald R
authors.initials: RR
authors.lastname: de Krijger
authors.forename: Rhiannon B
authors.initials: RB
authors.lastname: van Loenhout
authors.forename: Albert P
authors.initials: AP
authors.lastname: Bos
authors.forename: Job B M
authors.initials: JB
authors.lastname: van Woensel
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology / Q000503:physiopathology; D017209:Apoptosis; D001344:Autopsy; D053148:Caspase 3 / Q000032:analysis; D004314:Down Syndrome / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology*; D005333:Fetus; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000032:analysis; D008168:Lung / Q000378:metabolism / Q000473:pathology*
chemical_list: D007633:Keratins; D053148:Caspase 3