Acute lung injury edema fluid decreases net fluid transport across human alveolar epithelial type II cells
Acute lung injury edema fluid decreases net fluid transport across human alveolar epithelial type II cells
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DOI：
10.1074/jbc.m700821200
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发表时间：
2007-08-17
影响因子：
4.8
通讯作者：
Matthay, Michael A.
中科院分区：
文献类型：
--
作者：
Lee, Jae W.;Fang, Xiaohui;Matthay, Michael A.
大多数急性肺损伤（ALI）患者的肺泡液体清除率降低，这与较高的死亡率相关。几种机制可能导致肺泡液体清除率降低。在这项研究中，我们测试的假设，肺水肿液从患者的ALI可能会减少离子转运基因的表达，负责在原代培养的人肺泡上皮II型细胞的矢量液体运输。暴露于ALI肺水肿液后，主要钠和氯转运基因的基因拷贝数减少。通过Western印迹分析，α ENaC、α 1 Na、K-ATP酶和囊性纤维化跨膜传导调节因子的蛋白水平也降低。相反，几种炎性细胞因子的基因拷贝数显著增加。功能研究表明，与血浆相比，暴露于ALI肺水肿液的人肺泡II型细胞的净矢量液体转运减少（0.02 +/- 0.05 vs 1.31 +/- 0.56 μ l/cm 2/ h，p< 0.02）。p38 MAPK磷酸化抑制剂（SB 202190）部分逆转了水肿液对净液体转运以及主要离子转运蛋白基因和蛋白表达的影响。总之，来自ALI患者的肺泡水肿液诱导人肺泡II型上皮细胞中钠和氯转运基因和蛋白的显著减少，这种效应与人肺泡II型细胞单层中净矢量液体转运的减少相关。
Most patients with acute lung injury ( ALI) have reduced alveolar fluid clearance that has been associated with higher mortality. Several mechanisms may contribute to the decrease in alveolar fluid clearance. In this study, we tested the hypothesis that pulmonary edema fluid from patients with ALI might reduce the expression of ion transport genes responsible for vectorial fluid transport in primary cultures of human alveolar epithelial type II cells. Following exposure to ALI pulmonary edema fluid, the gene copy number for the major sodium and chloride transport genes decreased. By Western blot analyses, protein levels of alpha ENaC, alpha 1Na, K- ATPase, and cystic fibrosis transmembrane conductance regulator decreased as well. In contrast, the gene copy number for several inflammatory cytokines increased markedly. Functional studies demonstrated that net vectorial fluid transport was reduced for human alveolar type II cells exposed to ALI pulmonary edema fluid compared with plasma ( 0.02 +/- 0.05 versus 1.31 +/- 0.56 mu l/ cm2/ h, p< 0.02). An inhibitor of p38 MAPK phosphorylation ( SB202190) partially reversed the effects of the edema fluid on net fluid transport as well as gene and protein expression of the main ion transporters. In summary, alveolar edema fluid from patients with ALI induced a significant reduction in sodium and chloride transport genes and proteins in human alveolar epithelial type II cells, effects that were associated with a decrease in net vectorial fluid transport across human alveolar type II cell monolayers.