Differential response of the epithelium and interstitium in developing human fetal lung explants to hyperoxia.
Hyperoxia is closely linked with the development of chronic lung disease of prematurity (CLD), but the exact mechanisms whereby hyperoxia alters the lung architecture in the developing lung remain largely unknown. We developed a fetal human lung organ culture model to investigate (a) the morphologic changes induced by hyperoxia and (b) whether hyperoxia resulted in differential cellular responses in the epithelium and interstitium. The effects of hyperoxia on lung morphometry were analyzed using computer-assisted image analysis. The lung architecture remained largely unchanged in normoxia lasting as long as 4 d. In contrast, hyperoxic culture of pseudoglandular fetal lungs resulted in significant dilatation of airways, thinning of the epithelium, and regression of the interstitium including the pulmonary vasculature. Although there were no significant differences in Ki67 between normoxic and hyperoxic lungs, activated caspase-3 was significantly increased in interstitial cells, but not epithelial cells, under hyperoxic conditions. These changes show that exposure of pseudoglandular lungs to hyperoxia modulates the lung architecture to resemble saccular lungs.
Division of Child Health, University of Leicester, UK.
Porus
P
Bustani
Rachel
R
Hodge
Ananth
A
Tellabati
Juan
J
Li
Hitesh
H
Pandya
Sailesh
S
Kotecha
D017209:Apoptosis; D001808:Blood Vessels / Q000033:anatomy & histology / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D049109:Cell Proliferation; D048430:Cell Shape; D004848:Epithelium / Q000033:anatomy & histology / Q000378:metabolism*; D005260:Female; D005333:Fetus / Q000033:anatomy & histology / Q000502:physiology*; D005865:Gestational Age; D006801:Humans; D018496:Hyperoxia; D007633:Keratins / Q000378:metabolism; D008168:Lung / Q000033:anatomy & histology / Q000378:metabolism; D009924:Organ Culture Techniques; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011247:Pregnancy; D011897:Random Allocation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
D019408:Platelet Endothelial Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; D007633:Keratins; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases