Activation of the granule pool of the NADPH oxidase accelerates apoptosis in human neutrophils

被引:123
|
作者
Lundqvist-Gustafsson, H [1 ]
Bengtsson, T
机构
[1] Linkoping Univ, Fac Hlth Sci, Div Pathol 2, S-58185 Linkoping, Sweden
[2] Linkoping Univ, Fac Hlth Sci, Div Med Microbiol, S-58185 Linkoping, Sweden
关键词
reactive oxygen species; inflammation; DNA fragmentation; HL-60; cells; adenosine;
D O I
10.1002/jlb.65.2.196
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:196 / 204
页数:9
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