Aberrant lung structure, composition, and function in a murine model of Hermansky-Pudlak syndrome
Aberrant lung structure, composition, and function in a murine model of Hermansky-Pudlak syndrome
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DOI：
10.1152/ajplung.00024.2003
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发表时间：
2003-09-01
影响因子：
4.9
通讯作者：
Swank, RT
中科院分区：
文献类型：
--
作者：
Lyerla, TA;Rusiniak, ME;Swank, RT
Hermansky-Pudlak综合征（HPS）是一种遗传异质性遗传病，引起色素沉着和出血时间延长。HPS的另一个严重的临床问题是肺部病理的发展，这可能导致严重的肺部疾病和过早死亡。目前还没有治愈这种疾病的方法，而且此前也没有报道过HPS肺部异常的动物模型。HPS小鼠模型是Hps1（苍白耳）和Hps2（珍珠）基因纯合隐性的，表现出肺II型细胞的显著异常。突变体II型细胞和片层体明显增大，片层体充满表面活性剂。突变体的肺部积聚了过多的自体荧光色素。突变肺的空气空间含有与年龄相关的炎症细胞和泡沫巨噬细胞升高。体内肺迟滞性测量显示突变小鼠的肺功能异常。所有这些特征都与HPS患者的肺部病理相似。突变肺形态测定显示明显的肺气肿。这些突变小鼠为进一步研究HPS的肺部病理和治疗提供了模型。我们假设异常的II型细胞板层体结构/功能可能预测HPS患者未来的肺部病理。
Hermansky-Pudlak syndrome (HPS) is a genetically heterogeneous inherited disease causing hypopigmentation and prolonged bleeding times. An additional serious clinical problem of HPS is the development of lung pathology, which may lead to severe lung disease and premature death. No cure for the disease exists, and previously, no animal model for the HPS lung abnormalities has been reported. A mouse model of HPS, which is homozygously recessive for both the Hps1 ( pale ear) and Hps2 ( pearl) genes, exhibits striking abnormalities of lung type II cells. Type II cells and lamellar bodies of this mutant are greatly enlarged, and the lamellar bodies are engorged with surfactant. Mutant lungs accumulate excessive autofluorescent pigment. The air spaces of mutant lungs contain age-related elevations of inflammatory cells and foamy macrophages. In vivo measurement of lung hysteresivity demonstrated aberrant lung function in mutant mice. All these features are similar to the lung pathology described in HPS patients. Morphometry of mutant lungs indicates a significant emphysema. These mutant mice provide a model to further investigate the lung pathology and therapy of HPS. We hypothesize that abnormal type II cell lamellar body structure/ function may predict future lung pathology in HPS.