Defective surfactant secretion in a mouse model of Hermansky-Pudlak syndrome
Defective surfactant secretion in a mouse model of Hermansky-Pudlak syndrome
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DOI：
10.1165/rcmb.2004-0293oc
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发表时间：
2005-07-01
影响因子：
6.4
通讯作者：
Bates, SR
中科院分区：
文献类型：
--
作者：
Guttentag, SH;Akhtar, A;Bates, SR
人类Hermansky-Pudiak综合征（HPS）代表了与严重的进行性肺部疾病相关的溶酶体相关细胞器生物发生障碍家族。人类病例报告和HPS的小鼠模型，白耳/珍珠小鼠（ep/pe），在II型肺泡上皮细胞中表现出巨大的板层小体（GLB）。我们检测了ep/pe小鼠的表面活性蛋白和磷脂，以阐明GLB形成的过程。在ep/pe小鼠中，组织磷脂的2.8倍富集是由于从出生到成年的积累。与野生型小鼠（WT）相比，成年ep/pe小鼠的组织表面活性蛋白（SP）-B和-C增加，而SP-A和-D没有差异。与WT相比，来自成年ep/pe小鼠的大聚集体表面活性剂（LA）的磷脂、SP-B和SP-C减少，SP-A和-D无差异。尽管与WT相比，ep/pe动物的LA显示出总蛋白与总磷脂的比例增加，但表面张力未受损。分离的II型细胞的磷脂分泌表明，ep/pe细胞的基础分泌和刺激分泌与50%的WT细胞相似。总之，我们的数据表明，GLB的形成与表面活性剂材料的异常运输或回收无关。相反，分泌受损是ep/pe小鼠中GLB形成的重要组成部分。
Hermansky-Pudiak syndrome (HPS) in humans represents a family of disorders of lysosome-related organelle biogenesis associated with severe, progressive pulmonary disease. Human case reports and a mouse model of HPS, the pale ear/pearl mouse (ep/pe), exhibit giant lamellar bodies (GLB) in type II alveolar epithelial cells. We examined surfactant proteins and phospholipid from ep/pe mice to elucidate the process of GLB formation. The 2.8-fold enrichment of tissue phospholipids in ep/pe mice resulted from accumulation from birth through adulthood. Tissue surfactant protein (SP)-B and -C were increased in adult ep/pe mice compared with wildtype mice (WT), whereas SP-A and -D were not different. Large aggregate surfactant (LA) from adult ep/pe mice had decreased phospholipid, SP-B, and SP-C, with no differences in SP-A and -D compared with WT. Although LA from ep/pe animals exhibited an increased total protein-to-total phospholipid ratio compared with WT, surface tension was not compromised. Phospholipid secretion from isolated type II cells showed that basal and stimulated secretion from ep/pe cells were similar to 50% of WT cells. Together, our data indicate that GLB formation is not associated with abnormal trafficking or recycling of surfactant material. Instead, impaired secretion is an important component of GLB formation in ep/pe mice.