Herber-Jonat, Susanne and Mittal, Rashmi and Huppmann, Marceline and Hammel, Markus and Liebisch, Gerhard and Yildirim, Ali Oender and Eickelberg, Oliver and Schmitz, Gerd and de Angelis, Martin Hrabe and Flemmer, Andreas W. and Holzinger, Andreas (2013) Abca3 haploinsufficiency is a risk factor for lung injury induced by hyperoxia or mechanical ventilation in a murine model. PEDIATRIC RESEARCH, 74 (4). pp. 384-392. ISSN 0031-3998, 1530-0447
Full text not available from this repository. (Request a copy)Abstract
BACKGROUND: Heterozygous ATP-binding-cassette subfamily A member 3 (ABCA3) mutations are associated with neonatal respiratory complications. In an adult murine model, we investigated whether Abca3 haploinsufficiency is a predisposing factor for lung injury induced by hyperoxia or mechanical ventilation. METHODS: Abca3 haploinsufficient (Abca3(+/-)) and wild-type (WT) mice were prospectively randomized to 25 min of ventilation or 72 h of hyperoxia or left unchallenged in air. RESULTS: As compared with WT mice, unchallenged Abca3(+/-) mice had significantly decreased lung phosphatidylcholine (PC) and phosphatidylglycerol (PG) levels (P < 0.02) and decreased lung compliance (P < 0.05). When ventilated for 25 min, Abca3(+/-) mice demonstrated a significantly greater increase in bronchoalveolar lavage (BAL) interleukins (P <= 0.01) and lung wet to dry ratio (P < 0.005). Hyperoxia resulted in increased compliance (P < 0.05) and total lung capacity (TLC) (P = 0.01) only in the Abca3(+/-) mice, consistent with enlarged alveolar spaces. The ratio of PC to PG in BAL-relevant for surfactant dysfunction-was significantly elevated by oxygen exposure, with the greatest increase in Abca3(+/-) mice. CONCLUSION: In a murine model, Abca3 haploinsufficiency results in an altered biochemical and lung mechanical phenotype, as well as a greater lung injury induced by hyperoxia or mechanical ventilation. The inability to maintain a normal PC/PG ratio appears to play a key role.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TANDEM MASS-SPECTROMETRY; PULMONARY SURFACTANT; RESPIRATORY-DISTRESS; II CELLS; MUTATIONS; DEFICIENCY; DISEASE; PROTEIN; MICE; PHOSPHATIDYLGLYCEROL; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 30 Mar 2020 06:31 |
| Last Modified: | 30 Mar 2020 06:31 |
| URI: | https://pred.uni-regensburg.de/id/eprint/15928 |
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