ApoE-Deficient Mice on Cholate-Containing High-Fat Diet Reveal a Pathology Similar to Lung Sarcoidosis
ApoE-Deficient Mice on Cholate-Containing High-Fat Diet Reveal a Pathology Similar to Lung Sarcoidosis
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DOI：
10.2353/ajpath.2010.090857
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发表时间：
2010-03-01
影响因子：
6
通讯作者：
Bromme, Dieter
中科院分区：
文献类型：
--
作者：
Samokhin, Andriy O.;Buehling, Frank;Bromme, Dieter
结节病是一种病因不明的慢性疾病，其特征是在各个器官，特别是肺部形成非坏死性上皮样肉芽肿。缺乏反映人类疾病发病机制的适当动物模型是研究结节病的主要障碍之一。在本报告中，我们描述了食用含胆酸盐高脂饮食的 ApoE(-/-) 小鼠，其表现出类似于人类结节病的肉芽肿性肺部炎症。组织学分析显示，在接受含胆酸盐高脂饮食 16 周后，肉芽肿数量最多的小鼠中，约 40% 出现边界明确且非坏死性肉芽肿。肉芽肿含有CD4+和CD8+T细胞，肉芽肿中的大多数细胞对巨噬细胞标记物Mac-3表现出免疫反应性。具有上皮样细胞形态特征的细胞表达血管紧张素转换酶、骨桥蛋白和组织蛋白酶K，这些都是人类结节病肉芽肿中上皮样细胞和巨细胞的特征。在一些肺部也检测到了巨细胞和非特异性内含物，例如肖曼氏体和结晶沉积物。肉芽肿炎症导致进行性肺纤维化。从饮食中去除胆酸盐可以防止肺肉芽肿的形成。分析的小鼠肺肉芽肿和人类结节病肉芽肿之间观察到的相似性，以及导致纤维化的慢性疾病特征，表明该小鼠模型可能是研究结节病的有用工具。 （Am J Pathol 2010，176：1148-1156；DOI：10.2353/ajpath.2010.090857）
Sarcoidosis is a chronic disease of unknown etiology characterized by the formation of non-necrotizing epithelioid granulomas in various organs, especially in the lungs. The lack of an adequate animal model reflecting the pathogenesis of the human disease is one of the major impediments in studying sarcoidosis. in this report, we describe ApoE(-/-) mice on a cholate-containing high-fat diet that exhibit granulomatous lung inflammation similar to human sarcoidosis. Histological analysis revealed well-defined and non-necrotizing granulomas in about 40% of mice with the highest number of granulomas after 16 weeks on a cholate-containing high-fat diet. Granulomas contained CD4(+) and CD8(+) T cells, and the majority of the cells in granulomas showed immunoreactivity for the macrophage marker Mac-3. Cells with morphological features of epithelioid cells expressed angiotensin-converting enzyme, osteopontin, and cathepsin K, all characteristics of epithelioid and giant cells in granulomas of human sarcoidosis. Giant cells and nonspecific inclusions such as Schaumann's bodies and crystalline deposits were also detected in some lungs. Granulomatons inflammation resulted in progressive pulmonary fibrosis. Removal of cholate from the diet prevented the formation of lung granulomas. The observed similarities between the analyzed mouse lung granulomas and granulomas of human sarcoidosis, as well as the chronic disease character leading to fibrosis, suggest that this mouse model might be a useful tool to study sarcoidosis. (Am J Pathol 2010, 176:1148-1156; DOI: 10.2353/ajpath.2010.090857)