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

• Verfasst von: Zhu, Lin [VerfasserIn]
• Verfasst von: Dürr, Julia [VerfasserIn]
• Verfasst von: Zhou-Suckow, Zhe [VerfasserIn]
• Verfasst von: Wagner, Willi Linus [VerfasserIn]
• Verfasst von: Weinheimer, Oliver [VerfasserIn]
• Verfasst von: Salomon, Johanna J. [VerfasserIn]
• Verfasst von: Leitz, Dominik [VerfasserIn]
• Verfasst von: Konietzke, Philip [VerfasserIn]
• Verfasst von: Yu, Hong [VerfasserIn]
• Verfasst von: Ackermann, Maximilian [VerfasserIn]
• Verfasst von: Stiller, Wolfram [VerfasserIn]
• Verfasst von: Kauczor, Hans-Ulrich [VerfasserIn]
• Verfasst von: Mall, Marcus A. [VerfasserIn]
• Verfasst von: Wielpütz, Mark Oliver [VerfasserIn]
• Titel: µCT to quantify muco-obstructive lung disease and effects of neutrophil elastase knockout in mice
• Verf.angabe: 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
• E-Jahr: 2022
• Jahr: January 26, 2022
• Umfang: 11 S.
• Fussnoten: Gesehen am 29.09.2022
• Titel Quelle: Enthalten in: American journal of physiology / Lung cellular and molecular physiology
• Ort Quelle: Bethesda, Md. : Soc., 1989
• Jahr Quelle: 2022
• Band/Heft Quelle: 322(2022), 3 vom: März, Seite L401-L411
• ISSN Quelle: 1522-1504
• DOI: doi:10.1152/ajplung.00341.2021
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: lung imaging
• Sach-SW: microscopic computed tomography
• Sach-SW: mucin hypersecretion
• Sach-SW: muco-obstructive lung disease
• Sach-SW: transgenic mouse model
• K10plus-PPN: 1817804464

Abstract

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.