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1 Dept of Internal Medicine, University of Giessen, Giessen, and 2 Clinical Research Group "Chronic Airway Diseases", Dept of Internal Medicine, Philipps University Marburg, and 3 Dept of Clinical Chemistry and Molecular Diagnostics, Philipps-University Marburg, Marburg, Germany.
CORRESPONDENCE: R. Voswinckel, Dept of Internal Medicine, University of Giessen, Giessen, Germany. Fax: 49 6419942568. E-mail: robert.voswinckel@innere.med.uni-giessen.de
Keywords: Alveolarisation, lung development, pneumonectomy, pulmonary alveoli, regeneration
Received: January 14, 2004
Accepted June 5, 2004
This study was partially funded by the German Research Foundation.
A model of inducible expansion of the gas exchange area in adult mice would be ideal for the investigation of molecular determinants of airspace regeneration in vivo. Therefore, the post-pneumonectomy (post-PNX) compensatory lung growth in adult C57BL/6 mice was characterised in this study.
Mice underwent left-sided PNX. Right lung volume was assessed on days 1, 3, 5, 7, 10 and 21 after PNX, and total DNA and cellular proliferation of the right lung were determined. Lung histology was studied using immunohistochemistry and quantitatively characterised by detailed stereological investigations. Pulmonary function was assessed using a mouse body-plethysmograph.
Following PNX, right-lung volume rapidly restored the initial volume of left and right lung. Total DNA increased significantly over 21 days and equalled the total DNA amount of both lungs in the control mice. Septal cell proliferation significantly increased after PNX, and included endothelial cells, epithelial cells, smooth muscle cells and fibroblasts. Stereological investigations of left and right control lungs versus right lungs 21 days after PNX indicated complete restoration of body mass-specific alveolar surface area. Pulmonary function testing showed marked alteration at 3 days and normalisation at 21 days post-PNX.
In conclusion, well reproducible reconstitution of alveolar gas-exchange surface based on septal tissue expansion may be provoked by pneumonectomy in adult mice.
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