A study for pulmonary cell preservation and lung transplantation on functions of alveolar epithelial ion transport

在慢性肺气肿或肺纤维化患者中，肺上皮细胞发生不可逆性损伤。这些现象，再加上最近人口年龄的增加，是慢性呼吸衰竭数量增加的重要原因之一。1996年，我们建立了肺2型细胞的分离培养方法，并建立了肺2型细胞的主要功能--Na+-K+-ATPase活性的测定方法。1997年，我们尝试建立了一种更有效的肺2型细胞分离方法。虽然这种新的方法还没有建立，但我们可以分离出纯度在80%以上的肺2型细胞。然后，我们试图通过对肺细胞保存的研究，建立一种保持肺2型细胞活性的方法。比较本所建立的肺保存液EP4液和常用的Euro-Collins液(EC液)。当我们用肺泡液体清除率(AFC)检测肺泡上皮功能时，EP4维持肺泡上皮功能，而EC不能维持这种功能。因此，我们测试了类固醇对肺泡上皮细胞功能的影响。在本实验中，糖皮质激素增加了AFC。这是一个新的证据，表明类固醇不仅作为抗炎剂发挥作用，而且通过将肺泡液泵入肺间质来保护活体免受肺损伤。

In patients of chronic pulmonary emphysema or pulmonary fibrosis, pulmonary epithelial cells were irreversibly damaged. These phenomena, combined with recent advancing of age of population, are one of the important reasons for an increase in number of chronic respiratory failure. Therefore, we started to study whether transplantation of pulmonary type 2 cells are feasible for a therapy of impairment of pulmonary epithelial functions.In 1996, we established a method of separation and culture for pulmonary type 2 cells, and a method of measurement of activity of Na^+-K^+-ATPase, which is the main function of pulmonary type 2 cells.ln 1997, we tried to establish a more effective separation method of pulmonary type 2 cells using a cell sorter. Although, this new method has not been established yet, we could separate pulmonary type 2 cells with purity of more than 80 %.Then we tried to establish a method for keeping viability of pulmonary type 2 cells by studying pulmonary cellular preservation. We compared pulmonary preservation mediums EP4 solution, established by our institute, and Euro-Collins solution (EC), usual preservation medium. When we measured alveolar epithelial functions using Alveolar Fluid Clearance (AFC), EP4 maintained alveolar epithelial functions but EC could not maintain those.In lung injury models, we showed that cyclooxygenase inhibitor prevented the pulmonary vascular permeability. Therefore, we tested steroid for function of alveolar epithelial cells. In this experiment, gluco-corticoid increased AFC.This is a new evidence that steroid acts not only as an anti-inflammatory agent but to protect living body from lung injury by pumping up alveolar fluid to lung interstitial space.