Self-organizing pattern of subpleural alveolar ducts

Abstract

in this study we have utilized an optical clearing method to allow visualization of a heretofore undescribed subpleural acinar structural organization in the mammalian lung. the clearing method enables visualization of the lung structure deep below the visceral pleura in intact inflated lungs. In addition to confirming previous observations that the immediate subpleural alveoli are uniform in appearance, we document for the first time that the subpleural lung parenchyma is much more uniformly organized than the internal parenchyma. Specifically, we report that below the surface layer of alveoli, there is a striking parallel arrangement of alveolar ducts that all run perpendicular to the visceral pleural surface. A three dimensional visualization of alveolar ducts allowed for a calculation of the average inner to outer duct diameter ratio of 0.53 in these subpleural ducts. This unique, selforganizing parallel duct structure likely impacts both elastic recoil and the transmission of tethering forces in healthy and diseased lungs.Alveoli in the region just below the pleural surface have been examined by light microscopy since the 1930s 1-7 . These studies have often examined how the alveoli expand with lung inflation and how they might change with lung pathology. However, because light scattering from alveolar walls limits the depth of visualization with conventional light microscopy, there has always been some question as to whether this subpleural alveolar anatomy is representative of the structure throughout the lung. On the one hand the relatively thick visceral pleura forms a fixed boundary to one facet of an alveolus, and this must offer a level of constraint that is not present in internal alveoli. On the other hand, there are on the order of a dozen or so facets of an alveolus that are not constrained by being connected to the relatively thick pleura, so the degree to which the presence of a pleural boundary affects alveolar structure is not well understood. That there might be a difference in structural organization near the pleura was shown by a study where the mean airspace chord length was shown to be smaller when assessed closer to the visceral pleura 8 . Although it is clear from light microcopy that there are alveoli immediately under the pleural surface, there has been no information of how the alveolar duct might be oriented in this region. Traditionally, the terminal airways (respiratory bronchioles and alveolar ducts) are assumed to be somewhat randomly oriented in the lung. However, a random orientation would predict that a certain percentage of the ducts would run parallel to the pleural surface, a situation that would seem to be structurally and mechanically untenable.In the present work, we sought to address this anatomical issue by examining the subpleural terminal lung structure using confocal fluorescent microscopy of optically cleared lungs. The optical clearing method permits imaging in the mouse lung to depths exceeding 30 alveolar diameters into the lung, allowing optical serial section...

GM-CSF-dependent CD301b+ lung dendritic cells confer tolerance to inhaled allergens

“…In agreement with a previous report demonstrating that type 2 alveolar epithelial cells (AT2s) are the major source of GM-CSF 32 , 33 , we confirmed that Csf2 gene expression is detected in AT2 cells using previously published dataset 34 (Extended Data 5c). Consistent with these observations, we found that CD301b + cDC2s reside in the interstitium around alveolar ducts that are surrounded by alveoli 35 ( Fig. 4g ).…”

Deep 3D reconstruction of synchrotron X-ray computed tomography for intact lungs

“…at expiration (Fig. 5 b) that are about twice as larger as reported in prior work that analyzes 2D images of fixed inflated lungs (about 40 m) 36 , 37 . Furthermore, in this study, the maximum value of the alveolar diameters is > 120 m, which is three times larger than the reports.…”

Spherical alveolar shapes in live mouse lungs

“…In this study, synchrotron x-ray imaging directly lets us compare alveolar morphology between live and fixed lungs. Specifically, the alveolar morphology has been reported as polyhedral 5 – 7 with 40 ~ 58 μm diameter in fully inflated fixed lungs 20 – 22 . However, we reveal that alveolar morphology in live lungs shows spherical and 2 ~ 3 times the larger alveolar diameter (81.6 ± 18.2 μm) even at the expiration than reported in fixed lungs.…”