CD44抗体诱导急性髓性白血病细胞增殖抑制作用的研究

Proliferative inhibition of acute myelogenous leukemic cells induced by anti-CD44 antibodies

目的 探讨抗CD4 4抗体对白血病细胞增殖的影响 ,以及对T淋巴细胞介导的白血病细胞的细胞毒作用的影响 ;阐明抗CD4 4抗体的抗肿瘤效应机制。方法 利用3 H TdR掺入法检测肿瘤细胞的DNA合成 ;利用PI染色 流式细胞仪法分析肿瘤细胞的细胞周期变化 ;利用PKH2 +PI双染色 流式细胞仪法检测T淋巴细胞所介导的细胞毒作用。结果 抗CD4 4抗体可明显地抑制高表达CD4 4分子的急性髓性白血病MML 1细胞的增殖 ,并且利用抗GAM抗体交联抗CD4 4抗体后 ,可直接诱导Fas敏感的MML 1细胞的凋亡改变。另外 ,抗CD4 4抗体单独即可抑制IL 2激活的T淋巴细胞介导的细胞毒作用 ;协同抗CD2抗体后 ,其对IL 2激活的T淋巴细胞介导的细胞毒作用的抑制更加明显。结论 CD4 4分子的表达可能与肿瘤的发生发展有一定的关系。抗CD4 4抗体对MML 1细胞的增殖抑制作用 ,可能与启动了Fas系统所介导的凋亡信号有关。另外 ,抗CD4 4抗体对T淋巴细胞所介导的白血病细胞的细胞毒作用的抑制 ,可能与其部分地阻断了CD4

Objective To detect the effect of anti CD44 antibody on the proliferation of leukemic cells and cytotoxicity to leukemic cells mediated by T lymphocytes, and to elucidate the antitumour mechanism of anti CD44 antibody. Methods The DNA synthesis of leukemic cells treated by anti CD44 antibody was detected with TdR incorporation. The cytotoxicity of leukemic cells mediated by T lymphocytes treated by anti CD44 antibody alone or combined with anti CD3 antibody/anti CD2 antibody was detected with double staining flow cytometry. After anti CD44 antibodies on leukemic cells were ligated with anti GAM antibodies, the cell cycle of the leukemic cells was analyzed with PI staining flow cytometry. Results The leukemic MML 1 cells expressed high level CD44 molecule were treated by anti CD44 antibody, and their proliferation was obviously inhibited. The cell cycle change of Fas sensitive leukemic MML 1 cells was induced after ligation anti CD44 antibodies to tumor cells with anti GAM antibodies. This change was associated with an increase in the number of cells in G 0/G 1 phase and a reduction in number of cells in G 2/M phase, and apoptosis character of leukemic MML 1 cells was also induced as treated by anti Fas antibody. Also anti CD44 antibodies alone inhibited the cytotoxicity of leukemic MML 1 cells mediated by the IL 2 activated T lymphocyte, but when combined with anti CD2 antibodies the inhibitory on the cytotoxicity of the IL 2 activated T lymphocyte was significantly increased. Conclusion CD44 molecule expression might be related to tumor development. The proliferative inhibitory on leukemic MML 1 cells mediated by anti CD44 antibodies and Fas sensitive leukemic MML 1 cell apoptosis induced by anti GAM antibody ligation might be related to apoptosis signal transduction mediated by Fas system. The inhibitory effect of anti CD44 antibody on the cytotoxicity of leukemic MML 1 cells mediated by T lymphocyte might be due to the partial block of the expressions of CD44.