Self-differentiation of human fetal lung organ culture: the role of prostaglandins PGE2 and PGF2 alpha.
Addition of PGE2, but not PGF2 alpha, to fetal lung organ cultures accelerates the process of self-differentiation with increased dilatation of terminal airsacs and differentiation of the epithelial lining. Indomethacin reduces the endogenous production by organ cultures of PGE2, PGF2 alpha, 13,14-dihydro-15-keto-PGE2, and 13,14-dihydro-15-keto-PGF2 alpha and retards the process of self-differentiation. Prolonged exposure of cultures to indomethacin results in cell necrosis. Indomethacin inhibition of self-differentiation can be reversed and accelerated by the addition of PGE2. Addition of PGF2 alpha in the presence of indomethacin prevents indomethacin-associated cell necrosis but does not accelerate dilatation or differentiation beyond that of cultures in sera-free media without additions. We propose that the endogenous production of PGE2 is a key process in the mechanism of self-differentiation of human fetal lung in organ culture.
Hume
R
R
Department of Child Life and Health, University of Edinburgh, Scotland, U.K.
Kelly
R
R
Cossar
D
D
Giles
M
M
Hallas
A
A
Gourlay
M
M
Bell
J
J
D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D015237:Dinoprost / Q000502:physiology*; D015232:Dinoprostone / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells; D004848:Epithelium / Q000196:embryology / Q000502:physiology; D005333:Fetus / Q000502:physiology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D008168:Lung / Q000166:cytology / Q000196:embryology* / Q000502:physiology; D009924:Organ Culture Techniques
D015237:Dinoprost; D015232:Dinoprostone; D007213:Indomethacin