Histochemical and cellular changes accompanying the appearance of lung fibrosis in an experimental mouse model for Hermansky Pudlak syndrome.
Histochemical and cellular changes accompanying the appearance of lung fibrosis in an experimental mouse model for Hermansky Pudlak syndrome.
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DOI：
10.1007/s00418-010-0724-8
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发表时间：
2010-08
影响因子：
2.3
通讯作者：
Lyerla, Timothy
中科院分区：
文献类型：
--
作者：
Wang, Lingyan;Lyerla, Timothy
关键词：
Hermansky Pudlak综合征（HPS）是一种异质性隐性遗传疾病，随着年龄的增长，有发展为肺纤维化的趋势。具有影响单独囊泡运输途径的两个突变HPS基因的小鼠品系C57 BL/6-Hps 1 ep-Ap 3b 1 pe在幼年时表现出严重的肺异常，包括具有巨大板层体和泡沫状肺泡巨噬细胞（AM）的肺泡II型（ATII）细胞增大，这在组织学上很容易识别。在这项研究中，使用经典的组织学和生物化学方法研究了老年动物肺纤维化的外观。使用Masson三色染色，发现HPS双突变小鼠在约17月龄时发生肺纤维化，但Chediak Higashi综合征（C57 BL/6-Lyst bg-J-J，CHS）或C57 BL/6 J黑色对照（WT）小鼠没有发生肺纤维化，这通过羟脯氨酸分析证实。在双突变小鼠中，所有年龄段的支气管肺泡灌洗样本中TGF β1水平均升高，但WT或CHS小鼠均未升高，表明该实验品系存在纤维化前状态;使用免疫组织化学染色，AM对该细胞因子呈高度阳性。ATII细胞的前表面活性物质蛋白C染色显示这些细胞随着年龄的增长而重新分布和异形，但通过前表面活性物质蛋白C和α-平滑肌肌动蛋白的双重染色没有证据表明ATII细胞的上皮-间质转化。这项研究表明，HPS双突变小鼠品系发展间质性肺炎（HPSIP）超过1岁，这可能是由异常的ATII细胞和AM激活加剧。与突出的纤维化前异常，这种双突变体可能作为一个模型，HPS的干预治疗。
Hermansky Pudlak syndrome (HPS) is a heterogeneous recessive genetic disease with a tendency to develop lung fibrosis with aging. A mouse strain with two mutant HPS genes affecting separate vesicle trafficking pathways, C57BL/6-Hps1 ep-Ap3b1 pe, exhibits severe lung abnormalities at young ages, including enlarged alveolar type II (ATII) cells with giant lamellar bodies and foamy alveolar macrophages (AMs), which are readily identified histologically. In this study, the appearance of lung fibrosis in older animals was studied using classical histological and biochemical methods. The HPS double mutant mice, but not Chediak Higashi syndrome (C57BL/6-Lyst bg-J-J, CHS) or C57BL/6J black control (WT) mice, were found to develop lung fibrosis at about 17 months of age using Masson trichrome staining, which was confirmed by hydroxyproline analysis. TGF β1 levels were elevated in bronchial alveolar lavage samples at all ages tested in the double mutant, but not WT or CHS mice, indicative of a prefibrotic condition in this experimental strain; and AMs were highly positive for this cytokine using immunohistochemistry staining. Prosurfactant protein C staining for ATII cells showed redistribution and dysmorphism of these cells with aging, but there was no evidence for epithelial-mesenchymal transition of ATII cells by dual staining for prosurfactant C protein and α-smooth muscle actin. This investigation showed that the HPS double mutant mouse strain develops interstitial pneumonia (HPSIP) past 1 year of age, which may be initiated by abnormal ATII cells and exacerbated by AM activation. With prominent prefibrotic abnormalities, this double mutant may serve as a model for interventive therapy in HPS.
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DOI：
10.1152/ajplung.00024.2003
发表时间：
2003-09-01
影响因子：
4.9
作者：
Lyerla, TA;Rusiniak, ME;Swank, RT
通讯作者：
Swank, RT
影响因子：
20.3
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Feng, LJ;Novak, EK;Swank, RT
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Swank, RT
影响因子：
2.3
作者：
Yamada, Mizuho;Kuwano, Kazuyoshi;Kasper, Michael
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Kasper, Michael
DOI：
10.1165/rcmb.2004-0293oc
发表时间：
2005-07-01
影响因子：
6.4
作者：
Guttentag, SH;Akhtar, A;Bates, SR
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Bates, SR
DOI：
10.1152/ajplung.90594.2008
发表时间：
2010-02-01
影响因子：
4.9
作者：
Hoffman, A. M.;Shifren, A.;Ingenito, E. P.
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Ingenito, E. P.