Caspase-7 deficiency protects from endotoxin-induced lymphocyte apoptosis and improves survival
Caspase-7 deficiency protects from endotoxin-induced lymphocyte apoptosis and improves survival
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DOI：
10.1182/blood-2008-09-178038
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发表时间：
2009-03-19
期刊：
影响因子：
20.3
通讯作者：
Kanneganti, Thirumala-Devi
中科院分区：
文献类型：
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作者：
Lamkanfi, Mohamed;Moreira, Lilian O.;Kanneganti, Thirumala-Devi
脓毒症和内毒素休克时白细胞的广泛凋亡是导致这些疾病相关的高死亡率的重要机制。半胱氨酸天冬氨酸氨基转移酶抑制剂对内毒素诱导的淋巴细胞凋亡有保护作用，可提高存活率，但目前尚不清楚哪些半胱氨酸天冬氨酸酶介导了内毒素诱导的淋巴细胞凋亡和死亡。我们在此报道，在脂多糖注射的小鼠脾细胞中，凋亡执行者caspase-7被激活，提示caspase-7在淋巴细胞凋亡中起作用。事实上，caspase-7基因缺陷的小鼠对脂多糖诱导的淋巴细胞凋亡具有抵抗力，并且显著地免受脂多糖诱导的致死作用，而不依赖于血清细胞因子的过度产生。这些结果首次揭示了caspase-7在体内的非多余作用，并确认caspase-7抑制是caspase-7抑制剂保护内毒素诱导的死亡机制的一个组成部分。(血。2009；113：2742-2745)
Extensive apoptosis of leukocytes during sepsis and endotoxic shock constitutes an important mechanism linked to the excessive mortality associated with these disorders. Caspase inhibitors confer protection from endotoxin-induced lymphocyte apoptosis and improve survival, but it is not clear which caspases mediate lipopolysaccharide (LPS)-induced lymphocyte apoptosis and mortality. We report here that the apoptotic executioner caspase-7 was activated in the splenocytes of LPS-injected mice, suggesting a role for caspase-7 in lymphocyte apoptosis. Indeed, caspase-7-deficient mice were resistant to LPS-induced lymphocyte apoptosis and were markedly protected from LPS-induced lethality independently of the excessive production of serum cytokines. These results reveal for the first time a nonredundant role for caspase-7 in vivo and identify caspase-7 inhibition as a component of the mechanism by which caspase inhibitors protect from endotoxin-induced mortality. (Blood. 2009;113:2742-2745)