The interleukin 1 beta-converting enzyme, caspase 1, is activated during Shigella flexneri-induced apoptosis in human monocyte-derived macrophages
The interleukin 1 beta-converting enzyme, caspase 1, is activated during Shigella flexneri-induced apoptosis in human monocyte-derived macrophages
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DOI：
10.1128/iai.65.12.5165-5170.1997
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发表时间：
1997-12-01
影响因子：
3.1
通讯作者：
Zychlinsky, A
中科院分区：
文献类型：
--
作者：
Hilbi, H;Chen, YJ;Zychlinsky, A
细菌性痢疾的病原菌志贺菌在体外能迅速杀死人单核细胞源性巨噬细胞。野生tgpe福氏志贺菌，但不是一个无毒的衍生物，诱导人巨噬细胞凋亡的形态和末端脱氧核苷酸转移酶介导的dUTP-生物素缺口末端标记（TUNEL）。志贺氏菌介导的巨噬细胞死亡被胱天蛋白酶的肽抑制剂乙酰基-Tyr-Val-Ala-Asp-aldehyde（acetyl-YVAD-CHO）和乙酰基-Tyr-Val-Ala-Asp-chloromethylketone（acetyl-YVAD-CMK）阻断。在存在或不存在集落刺激因子（CSF）（如巨噬细胞-CSF或粒细胞-巨噬细胞-CSF）的情况下成熟的单核细胞中观察到YVAD对细胞凋亡的保护作用。此外，脂多糖（LPS）或γ干扰素（IFN-γ）使人巨噬细胞部分抵抗志贺氏菌的细胞毒性。用LPS或IFN-γ刺激的巨噬细胞也受到YVAD的保护，免受志贺氏菌诱导的细胞死亡。在志贺氏菌感染人类巨噬细胞期间，白细胞介素-1 β（IL-1 β）被裂解为成熟形式。IL-1 β成熟被YVAD严重延迟，表明IL-1 β转化酶（ICE;半胱天冬酶1）在志贺氏菌诱导的细胞凋亡中被激活。志贺氏菌通过激活ICE诱导人巨噬细胞凋亡的发现支持了这样的假设，即志贺氏菌病的急性炎症特征最初是由凋亡的巨噬细胞触发的，所述凋亡的巨噬细胞在程序性细胞死亡期间释放成熟的IL-1 β。
Shigella, the etiological agent of bacillary dysentery, rapidly kills human monocyte-derived macrophages in vitro. Wild-tgpe Shigella flexneri, but not a nonvirulent derivative, induced human macrophage apoptosis as determined by morphology and terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labelling (TUNEL). Shigella-mediated macrophage cell death was blocked by the peptide inhibitors of caspases, acetyl-Tyr-Val-Ala-Asp-aldehyde (acetyl-YVAD-CHO) and acetyl-Tyr-Val-Ala-Asp-chloromethylketone (acetyl-YVAD-CMK). Protection from apoptosis by YVAD, was observed in monocytes matured in the presence or absence of colony-stimulating factors (CSF) like macrophage-CSF or granulocyte-macrophage-CSF. Furthermore, lipopolysaccharide (LPS) or gamma interferon (IFN-gamma) rendered human macrophages partially resistant to Shigella cytotoxicity. Macrophages stimulated with either LPS or IFN-gamma were also protected by YVAD from Shigella-induced cell death. During Shigella infections of human macrophages, interleukin-1 beta (IL-1 beta) was cleaved to the mature form. IL-1 beta maturation was severely retarded by YVAD, indicating that IL-1 beta-converting enzyme (ICE; caspase 1) is activated in Shigella-induced apoptosis. The finding that Shigella induces apoptosis in human macrophages by activating ICE supports the hypothesis that the acute inflammation characteristic of shigellosis is initially triggered by apoptotic macrophages which release mature IL-1 beta during programmed cell death.