Salamone G, Giordano M, Trevani A S, Gamberale R, Vermeulen M, Schettinni J, Geffner J R
Laboratory of Immunology, Institute of Hematologic Research, National Academy of Medicine, Buenos Aires, Argentina.
J Immunol. 2001 Mar 1;166(5):3476-83. doi: 10.4049/jimmunol.166.5.3476.
We examined the ability of TNF-alpha to modulate human neutrophil apoptosis. Neutrophils cultured with TNF-alpha alone undergo a low but significant increase in the number of apoptotic cells. More interestingly, when neutrophils were pretreated with TNF-alpha for 1-2 min at 37 degrees C and then were exposed to a variety of agents such as immobilized IgG, IgG-coated erythrocytes, complement-treated erythrocytes, zymosan, PMA, zymosan-activated serum, fMLP, Escherichia coli, and GM-CSF for 3 h at 37 degrees C, a marked stimulation of apoptosis was observed. Similar results were obtained in neutrophils pretreated with TNF-alpha for 30 min, 1 h, 3 h, and 18 h. Dose-dependent studies showed that TNF-alpha enhances neutrophil apoptosis at concentrations ranging from 1 to 100 ng/ml. In contrast to the observations made in neutrophils pretreated with TNF-alpha, there was no stimulation of apoptosis when TNF-alpha was added to neutrophils previously activated by conventional agonists. Experiments performed to establish the mechanism through which TNF-alpha promotes neutrophil apoptosis showed that neither reactive oxygen intermediates nor the Fas/Fas ligand system appear to be involved. Our results suggest that TNF-alpha plays a critical role in the control of neutrophil survival by virtue of its ability to induce an apoptotic death program which could be triggered by a variety of conventional agonists.
我们研究了肿瘤坏死因子-α（TNF-α）调节人中性粒细胞凋亡的能力。单独用TNF-α培养的中性粒细胞凋亡细胞数量有少量但显著的增加。更有趣的是，当中性粒细胞在37℃用TNF-α预处理1 - 2分钟，然后在37℃暴露于多种试剂如固定化IgG、IgG包被的红细胞、补体处理的红细胞、酵母聚糖、佛波酯（PMA）、酵母聚糖激活的血清、N-甲酰甲硫氨酸-亮氨酸-苯丙氨酸（fMLP）、大肠杆菌和粒细胞-巨噬细胞集落刺激因子（GM-CSF）3小时时，观察到凋亡有明显的刺激作用。在用TNF-α预处理30分钟、1小时、3小时和18小时的中性粒细胞中也得到了类似结果。剂量依赖性研究表明，TNF-α在1至100 ng/ml的浓度范围内增强中性粒细胞凋亡。与用TNF-α预处理的中性粒细胞中的观察结果相反，当将TNF-α添加到先前由传统激动剂激活的中性粒细胞中时，没有凋亡刺激作用。为确定TNF-α促进中性粒细胞凋亡的机制而进行的实验表明，活性氧中间体和Fas/Fas配体系统似乎均未参与。我们的结果表明，TNF-α凭借其诱导可由多种传统激动剂触发的凋亡死亡程序的能力，在控制中性粒细胞存活中起关键作用。
