Dual mechanism for Mycobacterium tuberculosis cytotoxicity on lung epithelial cells
Dual mechanism for Mycobacterium tuberculosis cytotoxicity on lung epithelial cells
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DOI：
10.1139/w2012-067
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发表时间：
2012-07-01
影响因子：
2.8
通讯作者：
Quinn, Frederick D.
中科院分区：
文献类型：
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作者：
Castro-Garza, Jorge;Swords, W. Edward;Quinn, Frederick D.
结核分枝杆菌菌株CDC 1551和Erdman用于评估感染的A549人肺泡上皮细胞单层的细胞毒性。发现菌株CDC 1551诱导A549单层的定性破坏比菌株Erdman更大，尽管在感染过程中总细胞内和细胞相关细菌生长速率没有显著差异。来自用2 M.结核菌株对A549细胞产生细胞毒性作用，与受感染单核细胞释放的肿瘤坏死因子α（TNF-α）的量相关。向感染单核细胞培养物的上清液中加入TNF-α中和抗体确实防止了对覆盖有该混合物的A549细胞的细胞毒性作用的诱导，但当在用M感染之前加入时，不能防止上皮细胞的死亡。结核杆菌因此，这些数据与以前的观察一致，即肺上皮细胞感染M。结核杆菌在体外被迅速杀死。此外，数据表明，一些观察到的上皮细胞杀伤可能是附带损害;结核病感染的单核细胞
Mycobacterium tuberculosis strains CDC1551 and Erdman were used to assess cytotoxicity in infected A549 human alveolar epithelial cell monolayers. Strain CDC1551 was found to induce qualitatively greater disruption of A549 monolayers than was strain Erdman, although total intracellular and cell-associated bacterial growth rates over the course of the infections were not significantly different. Cell-free culture supernatants from human monocytic cells infected with either of the 2 M. tuberculosis strains produced a cytotoxic effect on A549 cells, correlating with the amount of tumor necrosis factor alpha (TNF-alpha) released by the infected monocytes. The addition of TNF-alpha-neutralizing antibodies to the supernatants from infected monocyte cultures did prevent the induction of a cytotoxic effect on A549 cells overlaid with this mixture but did not prevent the death of epithelial cells when added prior to infection with M. tuberculosis bacilli. Thus, these data agree with previous observations that lung epithelial cells infected with M. tuberculosis bacilli are rapidly killed in vitro. In addition, the data indicate that some of the observed epithelial cell killing may be collateral damage; the result of TNF-alpha released from M. tuberculosis-infected monocytes.