Activated T killer cells induce apoptosis in lung epithelial cells and the release of pro-inflammatory cytokine TNF-α
Activated T killer cells induce apoptosis in lung epithelial cells and the release of pro-inflammatory cytokine TNF-α
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DOI：
10.1002/eji.200425097
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发表时间：
2004-06-01
影响因子：
5.4
通讯作者：
Krammer, PH
中科院分区：
文献类型：
--
作者：
Shinbori, T;Walczak, H;Krammer, PH
细胞凋亡被认为参与了急性呼吸窘迫综合征和间质性肺炎中肺上皮细胞的损伤。细胞凋亡在人肺组织中的作用及其潜在的分子机制尚不清楚。为了解决这些问题，我们开发了一种体外实验，在SEB存在的情况下，将人肺上皮细胞系和葡萄球菌肠毒素B （SEB）反应性人CD8(+) CTL细胞系共培养。seb刺激的CD8(+) CTL主要通过穿孔素/颗粒酶介导途径诱导肺上皮细胞凋亡。在这些细胞中，凋亡最初独立于死亡受体途径。我们还测试了ifn - γ对肺上皮细胞凋亡的调节作用。在ifn - γ预处理的肺上皮细胞中，CD95 （APO-1/Fas）激活以及tnf相关凋亡诱导配体（TRAIL）受体和TNFR激活导致细胞凋亡。此外，我们发现seb刺激的CD8+ CTL与肺上皮细胞的相互作用诱导了tnf - α分泌的增加。这些结果表明细菌超抗原反应性CD8(+) CTL在诱导肺上皮细胞凋亡和调节肺组织炎症过程中起重要作用。
Apoptosis is thought to be involved in lung epithelial cell damage in acute respiratory distress syndrome and interstitial pneumonia. Both the role of apoptosis and its underlying molecular mechanisms in human lung tissue remain unclear. To address these issues, we developed an in vitro assay in which a human lung epithelial cell line and a staphylococcal enterotoxin B (SEB)-reactive human CD8(+) CTL line were co-cultured in the presence of SEB. SEB-stimulated CD8(+) CTL induced apoptosis in the lung epithelial cell line primarily through the perforin/granzyme-mediated pathway. In these cells, apoptosis was initially independent of death receptor pathways. We also tested the effect of IFN-gamma on modulation of apoptosis in lung epithelial cells. In IFN-gamma-pretreated lung epithelial cells, CD95 (APO-1/Fas) activation as well as TNF-related apoptosis-inducing ligand (TRAIL) receptor and TNFR activation led to apoptosis. Furthermore, we found that the interaction of SEB-stimulated CD8+ CTL with lung epithelial cells induced an increase in TNF-alpha secretion. These results suggest an important role for bacterial superantigen-reactive CD8(+) CTL in induction of lung epithelial cell apoptosis and in modulation of inflammatory processes in lung tissue.