Schneider Jan Philipp, Arkenau Martina, Knudsen Lars, Wedekind Dirk, Ochs Matthias
Institute of Functional and Applied Anatomy, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany; Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Hannover, Germany; REBIRTH Cluster of Excellence, Hannover, Germany.
Institute of Functional and Applied Anatomy, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany.
Ann Anat. 2017 May;211:158-175. doi: 10.1016/j.aanat.2017.01.013. Epub 2017 Feb 7.
Pulmonary surfactant, a mixture of lipids and proteins at the air-liquid interface of alveoli, prevents the lungs from collapsing due to surface tension. One constituent is surfactant-associated protein-D (SP-D), a protein involved in surfactant homeostasis and innate immunity. Mice deficient in SP-D (SP-D (-/-)) has been described as developing a characteristic phenotype which affects the surfactant system (including changes in the intra-cellular and intra-alveolar surfactant pool, alveolar epithelial type II cells and alveolar macrophages), lung architecture and its inflammatory state (development of an emphysema-like pathology, inflammatory cell infiltration). Furthermore, it has been described that these mice develop sub-pleural fibrosis and a thickening of alveolar septal walls. The aim of the present study was to systematically investigate the long term progression of this phenotype with special focus on parenchymal remodeling, whether there are progressive emphysematous changes and whether there is progressive septal wall thickening which might indicate the development of pulmonary fibrosis. By means of design-based stereology and light microscopy, lungs of wild type (wt) and SP-D (-/-) mice of four age groups (3, 6, 12 and ∼18 months) were investigated. The data do not suggest a relevant spontaneous pro-fibrotic remodeling or a destructive process in the aging SP-D (-/-) mice. We demonstrated neither a significant destructive emphysema nor significant thickening of alveolar septal walls, but the data suggest an increase in the number weighted mean alveolar volume in aging SP-D (-/-) mice without loss of alveoli or alveolar epithelial surface area per lung. This increase may reflect over-distension due to altered mechanical properties of alveoli. In the light of our findings and data from the literature, the question arises as to whether a lack of SP-D promotes structural changes in the lung which have been described as being associated with aging lungs. Furthermore, data from wt mice point to an ongoing alveolarization during adult life in C57Bl/6NCrl mice. Our data may promote further studies on the morphological development of the aging lung and the role of SP-D in this process.
肺表面活性物质是肺泡气液界面处的脂质和蛋白质混合物，可防止肺部因表面张力而塌陷。其中一种成分是表面活性物质相关蛋白-D（SP-D），一种参与表面活性物质稳态和固有免疫的蛋白质。缺乏SP-D的小鼠（SP-D (-/-)）已被描述为会出现一种特征性表型，该表型会影响表面活性物质系统（包括细胞内和肺泡内表面活性物质池、肺泡II型上皮细胞和肺泡巨噬细胞的变化）、肺结构及其炎症状态（出现类似肺气肿的病理改变、炎性细胞浸润）。此外，还描述了这些小鼠会出现胸膜下纤维化和肺泡间隔壁增厚。本研究的目的是系统地研究这种表型的长期进展情况，特别关注实质重塑、是否存在进行性肺气肿变化以及是否存在可能表明肺纤维化发展的进行性间隔壁增厚。通过基于设计的体视学和光学显微镜技术，对四个年龄组（3、6、12和约18个月）的野生型（wt）和SP-D (-/-)小鼠的肺进行了研究。数据并不表明衰老的SP-D (-/-)小鼠存在相关的自发性促纤维化重塑或破坏性过程。我们既未证明存在明显的破坏性肺气肿，也未证明肺泡间隔壁有明显增厚，但数据表明衰老的SP-D (-/-)小鼠数量加权平均肺泡体积增加，而每只肺的肺泡或肺泡上皮表面积并未减少。这种增加可能反映了由于肺泡机械性能改变导致的过度扩张。根据我们的研究结果和文献数据，就会产生一个问题，即缺乏SP-D是否会促进肺部出现与衰老肺相关的结构变化。此外，野生型小鼠的数据表明C57Bl/6NCrl小鼠在成年期会持续发生肺泡化。我们的数据可能会促进对衰老肺形态发育以及SP-D在此过程中的作用的进一步研究。
