Service of Infectious Diseases, Institute of Biomedicine of Sevilla, University Hospital Virgen del Rocío/CSIC/University of Sevilla, Av. Manuel Siurot s/n, 41013 Sevilla, Spain.
Microb Pathog. 2011 May;50(5):224-32. doi: 10.1016/j.micpath.2011.01.008. Epub 2011 Feb 1.
A growing body of evidence supports the notion that susceptible Acinetobacter baumannii strain ATCC 19606 induces human epithelial cells death. However, most of the cellular and molecular mechanisms associated with this cell death remain unknown, and also the degree of the cytotoxic effects of a clinical panresistant strain compared with a susceptible strain has never been studied. Due to the role of proinflammatory cytokine release, oxidative stress and cytosolic calcium increase in the cell death-induced by other Gram-negative bacteria, we investigated whether these intracellular targets were involved in the cell death induced by clinical panresistant 113-16 and susceptible ATCC 19606 strains. Data presented here show that 113-16 and ATCC 19606 induce time-dependent cell death of lung epithelial cells involving a perturbation of cytosolic calcium homeostasis with subsequent calpain and caspase-3 activation. Prevention of this cell death by TNF-α and interleukin-6 blockers and antioxidant highlights the involvement of proinflammatory cytokines and oxidative stress in this phenomenon. These results demonstrate the involvement of calpain calcium-dependent in cell death induced by A. baumannii and the impact of proinflammatory cytokines and oxidative stress in this cell death; it is noteworthy to stress that some mechanisms are less induced by the panresistant strain.
越来越多的证据支持这样一种观点，即易感性鲍曼不动杆菌菌株 ATCC 19606 诱导人上皮细胞死亡。然而，与这种细胞死亡相关的大多数细胞和分子机制仍然未知，而且临床泛耐药菌株与易感性菌株的细胞毒性作用程度也从未被研究过。由于促炎细胞因子释放、氧化应激和细胞溶质钙增加在其他革兰氏阴性菌诱导的细胞死亡中起作用，我们研究了这些细胞内靶点是否参与了临床泛耐药 113-16 株和易感性 ATCC 19606 株诱导的细胞死亡。这里呈现的数据表明，113-16 和 ATCC 19606 诱导肺上皮细胞的时间依赖性细胞死亡，涉及细胞溶质钙稳态的扰动，随后钙蛋白酶和半胱天冬酶-3 的激活。TNF-α和白细胞介素-6 阻滞剂以及抗氧化剂对这种细胞死亡的预防突出了促炎细胞因子和氧化应激在这一现象中的作用。这些结果表明钙依赖性钙蛋白酶参与了鲍曼不动杆菌诱导的细胞死亡，促炎细胞因子和氧化应激在这种细胞死亡中起作用；值得强调的是，一些机制在泛耐药菌株中诱导作用较小。
