Pathogenesis of interstitial pneumonia caused by abnormal transport of lung surfactant

为了探讨肺表面活性物质转运紊乱引起的间质性肺炎的发病机制，我们对Hermansky-Pudlak综合征动物模型Long Evans Cinnamon大鼠的肺进行了分析。肺泡II型细胞内巨大板层小体明显增大，肺表面活性物质明显升高。细胞表面活性物质的基础分泌受到抑制，而激动剂诱导的分泌则相反增强。腺载体介导的Rab38可以改善这些表面活性物质的异常。出乎意料的是，大鼠的肺部出现了肺气肿的变化。据推测，感染、空气污染和/或衰老等并发症是该病发展为间质性肺炎的主要遗传异常因素之一。

To investigate pathogenesis of interstitial pneumonia that is caused by perturbation of lung surfactant transport, we analyzed the lungs of Long Evans Cinnamon rats, an animal model of Hermansky-Pudlak syndrome. There were remarkably enlarged giant lamellar bodies and increased lung surfactant in alveolar type II cells. Basal secretion of surfactant from the cells was inhibited but agonist-induced secretion was reversely enhanced. Adenovector-mediated delivery of Rab38 ameliorated these surfactant abnormalities. Unexpectedly, the rat lungs showed emphysematous changes. It is suspected that complication with infection, air pollution, and/or aging would be necessary in addition to a primary genetic abnormality to develop interstitial pneumonia in the disease.