Nitric oxide synthase plays a signaling role in TCR-triggered apoptotic death.
Nitric oxide synthase plays a signaling role in TCR-triggered apoptotic death.
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DOI：
10.4049/jimmunol.161.12.6526
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发表时间：
1998-12
影响因子：
4.4
通讯作者：
Mark S. Williams-Mark S.-Williams-2205705637;S. Noguchi;P. Henkart;Yoichi Osawa
中科院分区：
文献类型：
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作者：
Mark S. Williams-Mark S.-Williams-2205705637;S. Noguchi;P. Henkart;Yoichi Osawa
在TCR触发的成熟T淋巴细胞死亡中测试了刺激的一氧化氮（NO）产生的功能作用。在纯化的外周血人T细胞母细胞或2B 4小鼠T细胞杂交瘤中，NO合酶（NOS）抑制剂以立体特异性和浓度依赖性方式阻断了固定化抗CD 3诱导的细胞凋亡。这种作用似乎是选择性的，因为抗Fas抗体或类固醇地塞米松诱导的凋亡不受NOS抑制剂的影响。TCR刺激的功能性Fas配体的表达被NOS抑制剂以立体特异性方式衰减，但这些化合物不抑制TCR刺激的IL-2分泌或CD 69表面表达。亚硝基化酪氨酸，一个稳定的标记NO的产生，免疫化学检测T细胞中使用流式细胞术。TCR信号诱导NO产生，通过硝基酪氨酸特异性染色的增加来测量。在2B 4细胞的裂解物中检测到NOS酶活性，并且Western印迹分析表明该活性是由于NOS的神经元亚型的表达。因此，T细胞具有在Ag信号传导后产生NO的能力，这可能影响成熟T淋巴细胞的信号转导、Fas配体表面表达和凋亡性细胞死亡。
A functional role for stimulated nitric oxide (NO) production was tested in the TCR-triggered death of mature T lymphocytes. In purified peripheral human T cell blasts or the 2B4 murine T cell hybridoma, apoptotic cell death induced by immobilized anti-CD3 was blocked by inhibitors of NO synthase (NOS) in a stereospecific and concentration-dependent manner. This effect appeared to be selective since apoptotic death induced by anti-Fas Ab or the steroid dexamethasone was not affected by NOS inhibitors. TCR-stimulated expression of functional Fas ligand was attenuated in a stereospecific manner by NOS inhibitors, but these compounds did not inhibit TCR-stimulated IL-2 secretion or CD69 surface expression. Nitrosylated tyrosines, a stable marker for NO generation, were immunochemically detected in T cells using flow cytometry. TCR signals induced NO production, as measured by an increase in nitrotyrosine-specific staining. NOS enzymatic activity was detected in lysates of 2B4 cells, and Western blot analysis suggests that the activity is due to expression of the neuronal isoform of NOS. Thus, T cells have the capacity to generate NO upon Ag signaling, which may affect signal transduction, Fas ligand surface expression, and apoptotic cell death of mature T lymphocytes.