title: Systemic hydrogen sulfide administration partially restores normal alveolarization in an experimental animal model of bronchopulmonary dysplasia.
abstract: Arrested alveolarization is the pathological hallmark of bronchopulmonary dysplasia (BPD), a complication of premature birth. Here, the impact of systemic application of hydrogen sulfide (H2S) on postnatal alveolarization was assessed in a mouse BPD model. Exposure of newborn mice to 85% O2 for 10 days reduced the total lung alveoli number by 56% and increased alveolar septal wall thickness by 29%, as assessed by state-of-the-art stereological analysis. Systemic application of H2S via the slow-release H2S donor GYY4137 for 10 days resulted in pronounced improvement in lung alveolarization in pups breathing 85% O2, compared with vehicle-treated littermates. Although without impact on lung oxidative status, systemic H2S blunted leukocyte infiltration into alveolar air spaces provoked by hyperoxia, and restored normal lung interleukin 10 levels that were otherwise depressed by 85% O2. Treatment of primary mouse alveolar type II (ATII) cells with the rapid-release H2S donor NaHS had no impact on cell viability; however, NaHS promoted ATII cell migration. Although exposure of ATII cells to 85% O2 caused dramatic changes in mRNA expression, exposure to either GYY4137 or NaHS had no impact on ATII cell mRNA expression, as assessed by microarray, suggesting that the effects observed were independent of changes in gene expression. The impact of NaHS on ATII cell migration was attenuated by glibenclamide, implicating ion channels, and was accompanied by activation of Akt, hinting at two possible mechanisms of H2S action. These data support further investigation of H2S as a candidate interventional strategy to limit the arrested alveolarization associated with BPD.
authors: Dept. of Lung Development and Remodelling, Max Planck Institute for Heart and Lung Research, Parkstrasse 1, D-61231 Bad Nauheim, Germany. rory.morty@mpi-bn.mpg.de.
authors: Alicia
authors: A
authors: Madurga
authors: Ivana
authors: I
authors: Mižíková
authors: Jordi
authors: J
authors: Ruiz-Camp
authors: István
authors: I
authors: Vadász
authors: Susanne
authors: S
authors: Herold
authors: Konstantin
authors: K
authors: Mayer
authors: Heinz
authors: H
authors: Fehrenbach
authors: Werner
authors: W
authors: Seeger
authors: Rory E
authors: RE
authors: Morty
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001997:Bronchopulmonary Dysplasia / Q000473:pathology*; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D006862:Hydrogen Sulfide / Q000627:therapeutic use*; D018496:Hyperoxia / Q000473:pathology*; D008168:Lung / Q000254:growth & development; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D009946:Organothiophosphorus Compounds / Q000494:pharmacology; D010100:Oxygen / Q000633:toxicity*; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects; D011650:Pulmonary Alveoli / Q000473:pathology; D013440:Sulfides / Q000494:pharmacology; D014945:Wound Healing / Q000187:drug effects
chemical_list: D016207:Cytokines; C529376:GYY 4137; D009025:Morpholines; D009946:Organothiophosphorus Compounds; D013440:Sulfides; D051057:Proto-Oncogene Proteins c-akt; C025451:sodium bisulfide; D010100:Oxygen; D006862:Hydrogen Sulfide
keywords: alveolar type II cell; gasotransmitter; inflammation; lung development