title: Prostaglandin production and metabolism in self-differentiating human fetal lung organ culture.
abstract: PGE2 and PGF2 alpha are released into the media of human fetal lung organ cultures in decreasing amounts with time. This decline in PGs is not due to culture failure or loss of synthetic capacity, which can be stimulated by fetal bovine serum, nor is it due to increased catabolism of PGE2 to 13,14-dihydro-15-keto-PGE2 (PGEM) or of PGF2 alpha to 13,14-dihydro-15-keto-PGF2 alpha (PGFM). Immunohistochemically reactive PGs are not retained within lung cells. Antisera against methyl-moximated derivatives of PGEM or PGFM and preceded by derivatization on tissue sections of PGs by methyl-moximation not only demonstrate the localization of PGEM and PGFM in epithelial cells and blood vessels, but also show an overall decline in immunoreactivity with time. In addition electron microscopy of uncultured fetal lung removed directly after termination reveals various degrees of mitochondrial damage and in some cases plasma membrane blebs which resolve during the period in culture and as fetal lung self-differentiates. It is proposed that oxidative and mechanical stresses, occurring during termination of pregnancy or tissue preparation, result in cell damage and increased lung prostaglandin production, which, although decreasing during culture as cells recover, is sufficient to trigger terminal self-differentiation.
authors.affiliation: Department of Child Health, University of Dundee, Scotland.
authors.forename: R
authors.initials: R
authors.lastname: Hume
authors.forename: J
authors.initials: J
authors.lastname: Bell
authors.forename: M
authors.initials: M
authors.lastname: Gourlay
authors.forename: M
authors.initials: M
authors.lastname: Giles
authors.forename: A
authors.initials: A
authors.lastname: Hallas
authors.forename: D
authors.initials: D
authors.lastname: Cossar
authors.forename: R
authors.initials: R
authors.lastname: Kelly
mesh_terms: D002454:Cell Differentiation / Q000502:physiology; D003470:Culture Media; D015237:Dinoprost / Q000096:biosynthesis*; D015232:Dinoprostone / Q000096:biosynthesis*; D005333:Fetus / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000196:embryology / Q000378:metabolism* / Q000648:ultrastructure; D009924:Organ Culture Techniques; D011863:Radioimmunoassay
chemical_list: D003470:Culture Media; D015237:Dinoprost; D015232:Dinoprostone