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重型再生障碍性贫血患者血清诱导淋巴细胞凋亡及PML蛋白表达
Serum from patients with severe aplastic anemia induces lymphocyte apoptosis and PML protein overexpression
【摘要】 用免疫荧光染色及Westernblot检测重型再障患者血清对正常人淋巴细胞凋亡的促进作用及早幼粒细胞白血病 (PML)蛋白表达的诱导作用 ,并进一步观察Caspase3,8抑制剂作用前后这两者的变化 ,以探讨再生障碍性贫血(再障 )患者淋巴细胞凋亡增加的机制。结果显示 ,10例重型再障患者血清作用后 ,淋巴细胞的凋亡率较正常人血清作用后明显增加 (P <0 0 5 )。同时 ,PML蛋白也明显高表达 (P <0 0 0 1) ,两者呈正相关 (r =0 919,P <0 0 0 1)。caspase8抑制剂可部分阻断再障患者血清的这种作用 ,但caspase3抑制剂不能阻断这种作用。以上结果提示重型再障患者血清可诱导淋巴细胞PML蛋白的高表达 ,从而导致淋巴细胞凋亡 ,caspase8可能参与了这一过程。
【Abstract】 To investigate the involvement of PML and apoptosis in the pathogenesis of aplastic anemia (AA), the expression of PML protein and apoptosis in lymphocytes were measured with western blot and immunofluorescent staining after incubation for 24 hours with serum of healthy individuals (controls, n=10) and of patients with severe AA (SAA, n=10). It was shown that after incubation with serum from SAA patients PML protein was overexpressed in both peripheral lymphocytes from a normal donor and in a B cell line established from cells of the same individual. The normal lymphocytes a greater proportion of cells showed apoptosis after incubation with serum from SAA patients than that of controls, which was correlated to the serum induced expression of PML. In addition, the induction of PML expression and apoptosis in lymphocytes by the serum was partly blocked by caspase 8 inhibitor, whereas no significant difference was found before and after caspase 3 inhibitor being added. These data suggested that some potential components in the serum of SAA patients affected lymphocytes not only upregulate PML protein, but also activate selectively caspase 8, causing apoptosis.
【Key words】 aplastic anemia; PML protein; apoptosis; caspase 3; Caspase 8;
- 【文献出处】 基础医学与临床 ,Basic Medical Sciences and Clinics , 编辑部邮箱 ,2002年06期
- 【分类号】R556
- 【被引频次】3
- 【下载频次】54