Activation of the granule pool of the NADPH oxidase accelerates apoptosis in human neutrophils
Activation of the granule pool of the NADPH oxidase accelerates apoptosis in human neutrophils
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DOI：
10.1002/jlb.65.2.196
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发表时间：
1999-02-01
影响因子：
5.5
通讯作者：
Bengtsson, T
中科院分区：
文献类型：
--
作者：
Lundqvist-Gustafsson, H;Bengtsson, T
氧化应激可诱导包括人中性粒细胞在内的多种细胞凋亡。我们的目的是确定是否活性氧（ROS）产生的激活中性粒细胞与加速凋亡。暴露中性粒细胞离子霉素或佛波酯肉豆蔻酸酯（PMA）诱导细胞内过氧化氢的产生盖快速启动凋亡，测量染色质浓缩，细胞收缩，和DNA片段。中性粒细胞活化与甲酰甲硫氨酰亮氨酰苯丙氨酸（fMLP）产生的主要是细胞外过氧化氢，并没有进行凋亡，外源性加入过氧化氢酶阻断剂叠氮化钠，诱导凋亡的程度相同，并与类似的动力学PMA和离子霉素，腺苷抑制离子霉素诱导的细胞内过氧化氢的产生和凋亡。无论是PMA，也不离子霉素引起二甲基亚砜分化的HL-60细胞，这是不能在细胞内过氧化氢的生产，而过氧化氢诱导凋亡更有效地在这些细胞比中性粒细胞的凋亡。我们认为活化的中性粒细胞利用细胞内形成的H2 O2进行自杀。
Oxidative stress induces apoptosis iu many types of cells, including human neutrophils. Our objective was to determine whether reactive oxygen species (ROS) produced by activated neutrophils are associated with accelerated apoptosis, Exposing neutrophils to ionomycin or phorbol myristate acetate (PMA) induced intracellular H2O2 production lid rapid onset of apoptosis, measured as condensed chromatin, cellular shrinkage, and DNA fragmentation. Neutrophils activated with formyl-methionyl-leucyl-phenylalanine (fMLP) generated mainly extracellular H2O2 and did not undergo apoptosis, Exogenously added H2O2, together with the catalase blocker sodium azide, induced apoptosis to the same extent and,with similar kinetics as PMA and ionomycin, Adenosine inhibited ionomycin-induced intracellular H2O2 production and apoptosis. Neither PMA nor ionomycin caused apoptosis in dimethyl sulfoxide-differentiated HL-60 cells, which are incapable of intracellular H2O2 production, whereas H2O2 induced apoptosis more efficiently in these cells than in neutrophils. We propose that activated neutrophils use intracellularly formed H2O2 to commit suicide.