Remodeling of alveolar septa after murine pneumonectomy

Abstract

In most mammals, removing one lung (pneumonectomy) results in the compensatory growth of the remaining lung. In mice, stereological observations have demonstrated an increase in the number of mature alveoli; however, anatomic evidence of the early phases of alveolar growth has remained elusive. To identify changes in the lung microstructure associated with neoalveolarization, we used tissue histology, electron microscopy, and synchrotron imaging to examine the configuration of the alveolar duct after murine pneumonectomy. Systematic histological examination of the cardiac lobe demonstrated no change in the relative frequency of dihedral angle components (Ends, Bends, and Junctions) (P Ͼ 0.05), but a significant decrease in the length of a subset of septal ends ("E"). Septal retraction, observed in 20 -30% of the alveolar ducts, was maximal on day 3 after pneumonectomy (P Ͻ 0.01) and returned to baseline levels within 3 wk. Consistent with septal retraction, the postpneumonectomy alveolar duct diameter ratio (Dout:Din) was significantly lower 3 days after pneumonectomy compared to all controls except for the detergenttreated lung (P Ͻ 0.001). To identify clumped capillaries predicted by septal retraction, vascular casting, analyzed by both scanning electron microscopy and synchrotron imaging, demonstrated matted capillaries that were most prominent 3 days after pneumonectomy. Numerical simulations suggested that septal retraction could reflect increased surface tension within the alveolar duct, resulting in a new equilibrium at a higher total energy and lower surface area. The spatial and temporal association of these microstructural changes with postpneumonectomy lung growth suggests that these changes represent an early phase of alveolar duct remodeling. electron microscopy; microstructure; regeneration; surface tension IN MOST MAMMALS, REMOVING one lung (pneumonectomy) results in the compensatory growth of the remaining lung (5, 20). In mice, compensatory growth results in an increase in the number of alveoli to near-baseline levels in 3 wk; 74% of the new alveoli are formed within 6 days of surgery (9). The mechanism responsible for this rapid alveolar remodeling is unknown.

Alveolar septal patterning during compensatory lung growth: Part II the effect of parenchymal pressure gradients

“…The lower panels show their counterparts in the case of detergent-rinsed rabbit alveolar ducts. Note that while the secondary septa appear normal in the upper panel, they collapse onto the primary septa in the case of detergent-rinsed lungs, which is very similar to the pneumonectomized case (Ysasi etal., 2015), Left and Middle panels are adapted from Bachofen etal.(1979). D out and D in denote the outer and inner diameter of alveolar duct, respectively; 2H indicates the thickness of interstitial space.…”

Single-Cell Transcriptional Profiling of Cells Derived From Regenerating Alveolar Ducts

“…The expansion of the remaining lung is not simple isotropic expansion as there is a commensurate increase in lung weight (3), cell number (4), and alveolar number (5). These observations indicate that post-pneumonectomy lung growth involves fundamental remodeling of the lung microarchitecture (6,7).…”

“…Finite element modeling has shown that mechanical stretch-the signal most commonly implicated as a trigger in compensatory growth (1,8)-is maximal in the subpleural alveolar ducts (9,10). In many subpleural alveolar ducts, postpneumonectomy morphometry has demonstrated a retraction of alveolar septa and an increase in alveolar duct diameter (7). The time course of septal retraction suggests that ductal dilatation is followed by scattered cellular proliferation (11), the septal migration of myofibroblasts (12), and subsequent septal thickening (7).…”

“…In many subpleural alveolar ducts, postpneumonectomy morphometry has demonstrated a retraction of alveolar septa and an increase in alveolar duct diameter (7). The time course of septal retraction suggests that ductal dilatation is followed by scattered cellular proliferation (11), the septal migration of myofibroblasts (12), and subsequent septal thickening (7). Ysasi et al have speculated that these events participate in the repartitioning of the dilated alveolar ducts (7).…”

“…The time course of septal retraction suggests that ductal dilatation is followed by scattered cellular proliferation (11), the septal migration of myofibroblasts (12), and subsequent septal thickening (7). Ysasi et al have speculated that these events participate in the repartitioning of the dilated alveolar ducts (7). Of note, histomorphometry has demonstrated no aggregates of proliferating cells, analogous to nonspecific inflammation or classic wound healing, within the remodeling alveolar duct septa (13).…”