The role of ceroid in lung and gastrointestinal disease in Hermansky-Pudlak syndrome.
The role of ceroid in lung and gastrointestinal disease in Hermansky-Pudlak syndrome.
复制标题
蜡样物质在赫曼斯基-普德拉克综合征肺部和胃肠道疾病中的作用。
DOI：
10.1007/978-1-4899-5339-1_20
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发表时间：
1989
影响因子：
--
通讯作者：
Harmon,K
中科院分区：
文献类型：
--
作者：
Witkop,CJ;Townsend,D;Bitterman,PB;Harmon,K
Hermansky-Pudlak综合征（HPS）中ceroid相关病变的研究表明，限制性肺部疾病和肉芽肿性胃肠道病变是最常见的，占患者死亡人数的60%。未发现免疫系统缺陷。组织学、超微结构和化学研究表明，HPS患者的组织细胞和相关巨噬细胞中积累了不可生物降解的类ceroid。目前还没有已知的ceroid降解途径。铈通过胞吐作用从细胞中排出。野生型和苍白耳小鼠用抑制胞吐的白细胞肽治疗后，在器官细胞中以与HPS相同的顺序积累ceroid。对无明显肺功能缺陷的年轻HPS患者进行灌洗，透射电镜检查巨噬细胞，并检测血小板衍生生长因子。巨噬细胞含有ceroid， 7/12的患者具有27+/-42单位的PDGF生物活性，而对照组的活性为零。将纯化的ceroid喂给从非吸烟对照组肺中灌洗的巨噬细胞。喂食前，不到5%的细胞含有一个或两个类似于ceroid的黄橙色自荧光小颗粒。饲喂后，大约20%的对照细胞摄入了类类固醇，但PDGF没有增加。免疫学和组织学研究以及巨噬细胞在肺纤维化之前产生的PDGF都指出巨噬细胞在这些病变中的核心作用。这些研究没有区分巨噬细胞是否从其他细胞摄取了ceroid，或者ceroid是否由HPS巨噬细胞本身产生。
Studies of ceroid associated lesions in Hermansky-Pudlak syndrome (HPS) indicate that restrictive lung disease and granulomatous gastrointestinal lesions are among the most frequent and account for 60% of the deaths of the patients. No defects in the immune system in HPS were found. Histological, ultrastructural and chemical studies show accumulation of non-biodegradable ceroid in tissue cells and associated macrophages of HPS patients. There is no known degradative pathway for ceroid. Ceroid is eliminated from cells by exocytosis. Wild type and pale eared mice treated with leupeptin, which inhibits exocytosis, accumulate ceroid in organ cells in the same sequence seen in HPS. Young HPS patients without significant pulmonary function deficits were lavaged, the macrophages examined by TEM and tested for platelet derived growth factor. Macrophages contained ceroid and 7/12 patients had 27+/-42 units of PDGF bioactivity compared to zero activity in controls. Purified ceroid was fed to macrophages lavaged from the lungs of non-smoking control subjects. Prior to feeding, less than 5% of cells contained one or two small yellow-orange autofluorescent granules resembling ceroid. After feeding, approximately 20% of control cells had ingested ceroid, but PDGF was not increased. The immunologic and histologic studies and the production of PDGF by macrophages which precedes lung fibrosis all point to a central role of the macrophage in these lesions. These studies did not distinguish whether the macrophages ingested ceroid from other cells, or whether ceroid is produced intrinsically by the HPS macrophage.