Department of Respiratory Medicine, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, PR China.
Respir Physiol Neurobiol. 2012 Jul 1;182(2-3):71-80. doi: 10.1016/j.resp.2012.05.012. Epub 2012 May 17.
Our previous study showed that seawater can cause lung tissue cell apoptosis; in the present study, the immunohistochemistry and Western blot analysis results demonstrated that Fas, FasL, and cleaved caspase-8 and caspase-3 were up-regulated in the rat lungs exposed to seawater. We found that seawater-induced human lung alveolar epithelial A549 cell apoptosis was concentration and time dependent. Moreover, seawater increased the expression of Fas, FasL, and cleaved caspase-8 and caspase-3 in A549 cells. The incubation of A549 cells in the presence of FasL-neutralising antibody (NOK-2) or caspase-8 inhibitor (Z-IETD-FMK) resulted in a decrease of seawater-induced cell apoptosis. NOK-2 inhibited Fas/FasL interaction and reduced the cleavage of caspase-8 and caspase-3, and Z-IETD-FMK blocked caspase-8 and caspase-3 activation. Seawater similarly produced a significant increase in rat alveolar type II cell apoptosis and expression of Fas and cleaved caspase-8. In summary, the Fas/FasL pathway involved in alveolar epithelial cell (AEC) apoptosis could be important in the pathogenesis of seawater-induced acute lung injury (SW-ALI).
我们之前的研究表明，海水可导致肺组织细胞凋亡；在本研究中，免疫组化和 Western blot 分析结果表明，在暴露于海水中的大鼠肺部，Fas、FasL、裂解 caspase-8 和 caspase-3 表达上调。我们发现海水诱导的人肺泡上皮 A549 细胞凋亡呈浓度和时间依赖性。此外，海水增加了 A549 细胞中 Fas、FasL 和裂解 caspase-8 和 caspase-3 的表达。在存在 FasL 中和抗体（NOK-2）或 caspase-8 抑制剂（Z-IETD-FMK）的情况下孵育 A549 细胞，可导致海水诱导的细胞凋亡减少。NOK-2 抑制 Fas/FasL 相互作用，减少 caspase-8 和 caspase-3 的裂解，Z-IETD-FMK 阻断 caspase-8 和 caspase-3 的激活。海水同样使大鼠肺泡 II 型细胞凋亡和 Fas 及裂解 caspase-8 的表达显著增加。总之，肺泡上皮细胞（AEC）凋亡中 Fas/FasL 途径可能在海水诱导的急性肺损伤（SW-ALI）发病机制中起重要作用。
