Significance of Reactive Oxygen Intermediates in Fas-mediated apoptosis.

活性氧中间体在 Fas 介导的细胞凋亡中的意义。

• 批准号: 08670862
• 负责人: KASAHARA Yoshihito
• 金额: $ 1.47万
• 依托单位: Kanazawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08670862/
• 关键词: apoptosis; reactive oxygen intermediates; Fas; neutrophil; autoimmune lymphoproliferative syndrome; Fas mutation; カタラーゼ

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.

1)使用来自慢性肉芽肿病（CGD）患者的细胞研究了Fas介导的细胞凋亡中活性氧中间体的参与，这些细胞没有活性氧中间体产生的能力。虽然抗Fas抗体处理诱导正常人细胞凋亡，但CGD细胞对抗Fas抗体具有抗性。过氧化氢酶显著抑制Fas介导的正常细胞凋亡，而过氧化氢诱导的CGD细胞凋亡。2）在两个以肝脾肿大、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组织增生综合征同胞中检测到Fas介导的细胞凋亡，这与Fas或Fas配体基因突变的lpr或gld小鼠的临床表现相似。两例患者的细胞显示Fas诱导的凋亡减少，Western blot分析检测到较小的异常Fas蛋白。结果表明，患者Fas基因第7内含子T → C点突变，导致患者Fas抗原胞内部分（包括死亡结构域）缺失，血I型患者TCR α + CD 4-CD 6- T细胞增多，家系分析显示母亲有相同的Fas突变。这些结果表明Fas介导的细胞凋亡在体内免疫稳态中的意义。

项目成果

H.Kanegane, Y.Kasahara, Y.Niida, A.Yachie, S.Sugii, K.Takatsu, N.Taniguchi, and T.Miyawaki: "Expression of L-selectin (CD62L) discriminates Th1- and Th2-like cytokine producing populations among human memory CD4^+ T cells" Immunology. 87. 186-190 (1996)

H.Kanegane、Y.Kasahara、Y.Niida、A.Yachie、S.Sugii、K.Takatsu、N.Taniguchi 和 T.Miyawaki：“L-选择素 (CD62L) 的表达可区分 Th1 和 Th2 样细胞因子

Y.Kasahara, T.Wada, Y.Niida, K.Ohta, H.Seki, T.Hashimoto, T.Miyawaki, S.Koizumi, N.Taniguchi.: "Novel Fas (CD95/APO-1) mutations in infants with lymphoproliferative disorders." Int.Immunol.10 (2). 195-202 (1998)

Y.Kasahara、T.Wada、Y.Niida、K.Ohta、H.Seki、T.Hashimoto、T.Miyawaki、S.Koizumi、N.Taniguchi.：“婴儿中的新型 Fas (CD95/APO-1) 突变

Y.Kasahara et al: "Novel Fas(CD95/APO-1)mutations in infants with a lymphoprollferative disorder" Int.Immunol.10(2). 195-202 (1998)

Y.Kasahara 等人：“淋巴组织增生性疾病婴儿中的新型 Fas(CD95/APO-1) 突变”Int.Immunol.10(2)。

東馬 智子, 笠原 善仁, 他: "アレルギー疾患にみられる好塩基球IgE結合状態のフローサイトメトリー法による評価." アレルギー. 45(7). 627-636 (1996)

Tomoko Touma、Yoshihito Kasahara 等人：“通过流式细胞术评估过敏性疾病中的嗜碱性粒细胞 IgE 结合状态”45(7) (1996)。

T.Tohma, Y.Kasahara et al.: "Flowcytometric estimation of IgE binding on blood basophils in patients with allergic diseases (in Japanese)" Allergy. 45 (7). 627-636 (1996)

T.Tohma、Y.Kasahara 等人：“过敏性疾病患者血液嗜碱性粒细胞上 IgE 结合的流式细胞术评估（日语）” 过敏。