Significance of Reactive Oxygen Intermediates in Fas-mediated apoptosis.

1)以慢性肉芽肿病(CGD)患者细胞为研究对象，研究了活性氧中间产物在Fas介导的细胞凋亡中的作用。尽管抗Fas抗体处理可诱导正常人细胞发生凋亡，但CGD细胞对抗Fas抗体有抵抗作用。过氧化氢酶可显著抑制Fas介导的正常细胞的凋亡，而过氧化氢则可诱导CGD细胞的凋亡。2)两个以肝脾肿大、淋巴结肿大、全血细胞减少、高丙种球蛋白血症为特征的自身免疫性淋巴增殖性综合征的同胞可检测到Fas介导的细胞凋亡，这与具有Fas或Fas配体基因突变的LPR或GLD小鼠的临床表现相似。免疫印迹分析显示，2例患者细胞Fas诱导的细胞凋亡减少，异常Fas蛋白表达减少。检测到患者Fas基因内含子7的T-C点突变，发现患者Fas抗原缺失包括死亡结构域在内的胞内部分。该突变使I型血患者TCRalphabeta+CD4-CD6-T细胞增多，家系分析显示母亲存在相同的Fas突变。提示Fas介导的细胞凋亡在体内免疫稳态中具有重要意义。

1) The involvement of reactive oxygen intermediates in Fas-mediated apoptosis was investigated using cells from patients with chronic granulomatous disease (CGD) that have no ability of reactive oxygen intermediates production. Although the treatments with anti-Fas antibody induced apoptosis of cells from normal subjects, cells from CGD were resistant to anti-Fas antibody. Catalase significantly inhibited Fas-mediated apoptosis of normal cells, on the other hands hydrogen peroxides induced apoptosis of CGD cells.2) Fas-mediated apoptosis was estimated in two siblings with autoimmune lymphoproliferative syndrome characterized with hepatosplenomegaly, lymphadenopathy, pancytopenia, hyper-gammagloblinemia, which is similar to clinicalmanifestations of lpr or gld mouse that have mutations of Fas or Fas ligand gene. Cells from two patients showed reduced Fas-induced apoptosis and smaller abnormal Fas protein was detected by western blot analysis. The T to C point mutation of intron 7 in patients Fas gene was detected and Fas antigen of patients lacks intracellular portion including death domain by this mutation TCRalphabeta+CD4-CD6- T cells were increased in blood I patients and analysis of family showed that mother has a same Fas mutation. These results indicated significance of Fas-mediated apoptosis in immunological homeostasis n vivo.