Involvement of reactive oxygen intermediates in spontaneous and CD95(Fas/APO-1)-mediated apoptosis of neutrophils
Involvement of reactive oxygen intermediates in spontaneous and CD95(Fas/APO-1)-mediated apoptosis of neutrophils
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DOI：
10.1182/blood.v89.5.1748.1748_1748_1753
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发表时间：
1997-03-01
期刊：
影响因子：
20.3
通讯作者：
Taniguchi, N
中科院分区：
文献类型：
--
作者：
Kasahara, Y;Iwai, K;Taniguchi, N
众所周知，细胞凋亡是由氧化应激介导的。为了评估中性粒细胞产生的活性氧中间体（ROI）的功能作用，我们比较了从正常供体和慢性肉芽肿病（CGD）患者中分离的中性粒细胞的凋亡率，CGD是一种产生ROI的遗传缺陷。与正常中性粒细胞相比，体外培养的CGD中性粒细胞自发性细胞死亡明显受到抑制。抗fas单克隆抗体（MoAb）对CGD中性粒细胞凋亡的加速作用明显慢于正常中性粒细胞。这些发现提示中性粒细胞的凋亡可能是由内源性氧化产物介导的。通过观察发现，降低细胞内过氧化氢（H2O2）水平可显著抑制正常中性粒细胞的凋亡，证实了这一观点。添加过氧化氢酶对正常中性粒细胞凋亡的抑制作用与抗fas MoAb的存在无关。与正常中性粒细胞相比，H2O2增加了CGD中性粒细胞的自发凋亡和fas介导的凋亡。虽然介导中性粒细胞凋亡的几个因素仍有待确定，但这些结果表明，ROI是中性粒细胞凋亡的主要介质，并可能参与fas介导的信号转导途径，(C) 1997年由美国血液学学会。
Apoptosis is well known to be mediated by oxidative stress, To evaluate the functional role of reactive oxygen intermediates (ROI) produced by neutrophils, we compared the rates of apoptosis in neutrophils isolated from normal donors and from patients with chronic granulomatous disease (CGD), a hereditary defect in ROI production. Spontaneous cell death in CGD neutrophils in vitro was significantly inhibited relative to normal neutrophils. The acceleration of apoptosis induced by anti-fas monoclonal antibody (MoAb) in CGD neutrophils was much slower than that seen in normal neutrophils. These findings suggest that the apoptosis of neutrophils may be mediated by endogenous oxidative products. This suggestion was confirmed by observation that apoptosis of normal neutrophils was markedly inhibited by reduction of intracellular levels of hydrogen peroxide (H2O2). The inhibition of apoptosis in normal neutrophils by adding catalase occurred regardless of the presence of anti-fas MoAb. H2O2 increased both spontaneous apoptosis and Fas-mediated apoptosis of the CGD neutrophils in proportion to that seen in normal neutrophils. Although several factors that mediate the apoptosis of neutrophils remain to be determined, these results suggest that ROI are major mediators of the apoptosis in neutrophils and may be involved in Fas-mediated signal transduction pathway, (C) 1997 by The American Society of Hematology.