Normal surfactant pool sizes and inhibition-resistant surfactant from mice that overexpress surfactant protein A
Normal surfactant pool sizes and inhibition-resistant surfactant from mice that overexpress surfactant protein A
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DOI：
10.1165/ajrcmb.21.3.3676
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发表时间：
1999-09-01
影响因子：
6.4
通讯作者：
McCormack, FX
中科院分区：
文献类型：
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作者：
Elhalwagi, BM;Zhang, M;McCormack, FX
据报道，肺表面活性剂蛋白-A (SPA) 可调节 II 型肺泡细胞对表面活性剂的摄取和分泌，稳定包括肾小管髓磷脂在内的大型表面活性剂聚集体，并保护表面活性剂的表面活性免受蛋白质抑制剂的影响。在这项研究中，我们研究了 SP-A 过度表达对转基因小鼠肺稳态和表面活性剂功能的影响。人 SP-C 启动子用于指导大鼠肺泡 II 型细胞和远端呼吸道上皮非纤毛细支气管细胞中表面活性蛋白 A (rSP-A) 的合成。通过酶联免疫吸附测定测定，rSP-A 小鼠的肺匀浆和肺泡灌洗液中的 SP-A 水平比转基因阴性同窝小鼠高 7 至 8 倍。携带转基因的小鼠的游泳运动耐量和肺顺应性没有变化。通过形态分析，在随机选择的光学显微镜视野中观察到的平均气隙大小在转基因阳性和阴性小鼠中没有显着差异，但 15% 的转基因动物具有包含扩张的肺泡和肺泡管的散在病灶，没有炎症或纤维化的证据。一些肺泡巨噬细胞含有条形嗜渗包涵体，具有高度有序的超微结构。转基因阳性和阴性小鼠的组织或肺泡池的饱和磷脂酰胆碱大小或肺泡表面活性剂的大聚集体组成没有差异。从 rSP-A 小鼠中分离出的表面活性剂的表面活性与对照组相似，但在蛋白质抑制剂存在下，rSP-A 表面活性剂的表面张力降低特性得到了更好的保留（P < 0.05）。我们得出的结论是，SP-A 的过度表达不会影响静息表面活性剂磷脂水平，但它增强了表面活性剂对蛋白质抑制的抵抗力。
Pulmonary surfactant protein-A (SPA) has been reported to regulate the uptake and secretion of surfactant by alveolar type II cells, to stabilize large surfactant aggregates including tubular myelin, and to protect the surface activity of surfactant from protein inhibitors. In this study we investigated the consequences of overexpression of SP-A on pulmonary homeostasis and surfactant function in transgenic mice. The human SP-C promoter was used to direct synthesis of rat surfactant protein A (rSP-A) in alveolar type II cells and nonciliated bronchiolar cells of the distal respiratory epithelium. Levels of SP-A measured through enzyme-linked immunosorbent assay were 7- to 8-fold higher in lung homogenates and alveolar lavage fluid of the rSP-A mice than in those of transgene-negative littermates. The swimming exercise tolerance and lung compliance of mice bearing the transgene were unchanged. Mean air space sizes seen in randomly selected Light-microscopic fields were not significantly different in the transgene-positive and -negative mice by morphometric analysis, but 15% of transgenic animals had scattered foci containing dilated alveoli and alveolar ducts without evidence of inflammation or fibrosis. Some alveolar macrophages contained bar-shaped osmophilic inclusions that had a highly ordered ultrastructure. There were no differences between the transgene-positive and -negative mice in the tissue or alveolar pool sizes of saturated phosphatidylcholine or in the large-aggregate composition of alveolar surfactant. The surface activity of surfactant isolated from the rSP-A mice was similar to that of the controls, but in the presence of protein inhibitors, the surface tension-reducing properties of the rSP-A surfactant were better preserved (P < 0.05). We conclude that overexpression of SP-A does not affect resting surfactant phospholipid levels, but that it enhances the resistance of surfactant to protein inhibition.