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µCT to quantify muco-obstructive lung disease and effects of neutrophil elastase knockout in mice

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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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Main Authors: Zhu, Lin (Author) , Dürr, Julia (Author) , Zhou-Suckow, Zhe (Author) , Wagner, Willi Linus (Author) , Weinheimer, Oliver (Author) , Salomon, Johanna J. (Author) , Leitz, Dominik (Author) , Konietzke, Philip (Author) , Yu, Hong (Author) , Ackermann, Maximilian (Author) , Stiller, Wolfram (Author) , Kauczor, Hans-Ulrich (Author) , Mall, Marcus A. (Author) , Wielpütz, Mark Oliver (Author)
Format: Article (Journal)
Language:English
Published: January 26, 2022
In: American journal of physiology. Lung cellular and molecular physiology
Year: 2022, Volume: 322, Issue: 3, Pages: L401-L411
ISSN:1522-1504
DOI:10.1152/ajplung.00341.2021
Online Access: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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Author Notes: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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Summary: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.
Item Description:Gesehen am 29.09.2022
Physical Description:Online Resource
ISSN:1522-1504
DOI:10.1152/ajplung.00341.2021

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