µCT to quantify muco-obstructive lung disease and effects of neutrophil elastase knockout in mice
Muco-obstructive lung diseases are characterized by airway obstruction and hyperinflation, which can be quantified by imaging. Our aim was to evaluate µCT for longitudinal quantification of muco-obstructive lung disease in β-epithelial Na+ channel overexpressing (Scnn1b-TG) mice and of the effects o...
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| Hauptverfasser: | , , , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
January 26, 2022
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| In: |
American journal of physiology. Lung cellular and molecular physiology
Year: 2022, Jahrgang: 322, Heft: 3, Pages: L401-L411 |
| ISSN: | 1522-1504 |
| DOI: | 10.1152/ajplung.00341.2021 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1152/ajplung.00341.2021 Verlag, lizenzpflichtig, Volltext: https://journals.physiology.org/doi/full/10.1152/ajplung.00341.2021 
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| Verfasserangaben: | Lin Zhu, Julia Duerr, Zhe Zhou-Suckow, Willi Wagner, Oliver Weinheimer, Johanna Salomon, Dominik Leitz, Philip Konietzke, Hong Yu, Maximilian Ackermann, Wolfram Stiller, Hans-Ulrich Kauczor, Marcus A. Mall, Mark O. Wielpütz |
MARC
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| 245 | 1 | 0 | |a µCT to quantify muco-obstructive lung disease and effects of neutrophil elastase knockout in mice |c Lin Zhu, Julia Duerr, Zhe Zhou-Suckow, Willi Wagner, Oliver Weinheimer, Johanna Salomon, Dominik Leitz, Philip Konietzke, Hong Yu, Maximilian Ackermann, Wolfram Stiller, Hans-Ulrich Kauczor, Marcus A. Mall, Mark O. Wielpütz |
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| 246 | 3 | 3 | |a MuCT to quantify muco-obstructive lung disease and effects of neutrophil elastase knockout in mice |
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| 520 | |a Muco-obstructive lung diseases are characterized by airway obstruction and hyperinflation, which can be quantified by imaging. Our aim was to evaluate µCT for longitudinal quantification of muco-obstructive lung disease in β-epithelial Na+ channel overexpressing (Scnn1b-TG) mice and of the effects of neutrophil elastase (NE) knockout on its progression. Lungs from wild-type (WT), NE−/−, Scnn1b-TG, and Scnn1b-TG/NE−/− mice were scanned with 9-µm resolution at 0, 5, 14, and 60 days of age, and airway and parenchymal disease was quantified. Mucus adhesion lesions (MAL) were persistently increased in Scnn1b-TG compared with WT mice from 0 days (20.25 ± 6.50 vs. 9.60 ± 2.07, P < 0.05), and this effect was attenuated in Scnn1b-TG/NE−/− mice (5.33 ± 3.67, P < 0.001). Airway wall area percentage (WA%) was increased in Scnn1b-TG mice compared with WT from 14 days onward (59.2 ± 6.3% vs. 49.8 ± 9.0%, P < 0.001) but was similar in Scnn1b-TG/NE−/− compared with WT at 60 days (46.4 ± 9.2% vs. 45.4 ± 11.5%, P = 0.97). Air proportion (Air%) and mean linear intercept (Lm) were persistently increased in Scnn1b-TG compared with WT from 5 days on (53.9 ± 4.5% vs. 30.0 ± 5.5% and 78.82 ± 8.44 µm vs. 65.66 ± 4.15 µm, respectively, P < 0.001), whereas in Scnn1b-TG/NE−/−, Air% and Lm were similar to WT from birth (27.7 ± 5.5% vs. 27.2 ± 5.9%, P = 0.92 and 61.48 ± 9.20 µm vs. 61.70 ± 6.73 µm, P = 0.93, respectively). Our results suggest that µCT is sensitive to detect the onset and progression of muco-obstructive lung disease and effects of genetic deletion of NE on morphology of airways and lung parenchyma in Scnn1b-TG mice, and that it may serve as a sensitive endpoint for preclinical studies of novel therapeutic interventions for muco-obstructive lung diseases. | ||
| 650 | 4 | |a lung imaging | |
| 650 | 4 | |a microscopic computed tomography | |
| 650 | 4 | |a mucin hypersecretion | |
| 650 | 4 | |a muco-obstructive lung disease | |
| 650 | 4 | |a transgenic mouse model | |
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