Neoalveolarisation contributes to compensatory lung growth following pneumonectomy in mice.

Regeneration of the gas exchange area by induction of neoalveolarisation would greatly improve therapeutic options in destructive pulmonary diseases. Unilateral pneumonectomy is an established model to remove defined portions of gas exchange area and study mechanisms of compensatory lung growth. The question of whether new alveoli are added to the residual lung after pneumonectomy in mice was addressed. Left-sided pneumonectomy was performed in 11 adult C57BL/6 mice. Alveolar numbers were analysed in lungs fixed at days 6 and 20 after pneumonectomy and in 10 age-matched controls using design-based stereology based on a physical fractionator. Post-fixation lung volume was determined by fluid displacement. Complete restoration of lung volume was observed 20 days after pneumonectomy. Alveolar numbers were significantly increased by 33% in residual right lungs at day 20 in comparison with control right lungs. In control left lungs, an average of 471+/-162 x 10(3) alveoli was estimated, 49% of which were regenerated by residual lungs at day 20. Of the newly formed alveoli seen at day 20, 74% were already present at day 6. The present data demonstrate that, in addition to growth in size of existing alveoli, neoalveolarisation contributes to restoration of the gas exchange area in adult mice and is induced early after pneumonectomy.

Characterisation of post-pneumonectomy lung growth in adult mice.

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.