Yamamoto T, Iwasaki T, Watanabe N, Oshimi K, Naito M, Tsuruo T, Kobayashi Y
Department of Biomolecular Science, Faculty of Science, Toho University, Chiba, Japan.
Blood. 1993 Mar 1;81(5):1342-6.
Some patients with granular lymphocyte-proliferative disorders (GLPD) have been reported to have an aggressive clinical course with a poor prognosis and to be refractory to chemotherapy. In this study, expression of multidrug resistance P-glycoprotein on peripheral blood mononuclear cells (PBMC) of 11 patients with GLPD was examined by staining with MRK 16, a monoclonal antibody that binds to an external epitope of P-glycoprotein, and with the dye rhodamine, a known substance to be excreted from the cells through P-glycoprotein. Among those tested, the PBMC of six of eight patients with T-cell-type GLPD as well as those of three of three patients with natural killer cell-type GLPD expressed P-glycoprotein significantly. Furthermore, PBMC of two of two patients were also poorly stained with the dye rhodamine, and the treatment of PBMC with either verapamil or quinidine, multidrug resistance-reversing agents, led to their increased staining, suggesting that these PBMC actively release chemotherapeutic agents.
据报道,一些颗粒淋巴细胞增殖性疾病(GLPD)患者临床病程进展迅速,预后较差,且对化疗耐药。在本研究中,采用与P-糖蛋白外部表位结合的单克隆抗体MRK 16及已知通过P-糖蛋白从细胞排出的染料罗丹明进行染色,检测了11例GLPD患者外周血单个核细胞(PBMC)上多药耐药P-糖蛋白的表达。在检测的患者中,8例T细胞型GLPD患者中的6例以及3例自然杀伤细胞型GLPD患者中的3例的PBMC均显著表达P-糖蛋白。此外,2例患者的PBMC对罗丹明染料的染色也较差,用多药耐药逆转剂维拉帕米或奎尼丁处理PBMC后,其染色增加,提示这些PBMC可主动释放化疗药物。