Coon J S, Wang Y Z, Bines S D, Markham P N, Chong A S, Gebel H M
Department of Pathology, Rush Presbyterian St. Luke's Medical Center, Chicago, Illinois.
Hum Immunol. 1991 Oct;32(2):134-40. doi: 10.1016/0198-8859(91)90110-u.
The multidrug resistance gene (mdr1) is a member of the recently described ATP binding cassette (ABC) superfamily of transporters. Family members include: (1) the cystic fibrosis transmembrane conductance regulator gene; (2) the hlyB gene of bacteria, and (3) the histocompatibility antigen modifier (HAM) gene. The level of expression of mdr1 correlates with multidrug resistance (MDR), the ability of cells to efflux otherwise toxic doses of several chemotherapeutic agents. MDR activity is also associated with the efflux of cationic lipophilic compounds such as the fluorescent dye rhodamine 123. Recently it was reported that normal lymphocytes efflux rhodamine 123, suggesting that these cells possess MDR-like activity due to the expression of mdr1. In this study, using two-color flow cytometric analysis, we observed that the ability to efflux rhodamine 123 was heterogeneous among human lymphocyte subsets in the order of CD8 greater than CD4 greater than CD2O. Rhodamine 123 efflux and accumulation in lymphocytes was sensitive to the known MDR reversing agents, verapamil and Solutol HS 15. Collectively, these data suggest that an MDR-like transport system is present in normal lymphocytes and may be important for trafficking of molecules involved in lymphocyte function.
多药耐药基因（mdr1）是最近描述的转运蛋白ATP结合盒（ABC）超家族的成员。该家族成员包括：（1）囊性纤维化跨膜传导调节基因；（2）细菌的hlyB基因，以及（3）组织相容性抗原修饰基因（HAM）。mdr1的表达水平与多药耐药性（MDR）相关，即细胞排出几种化疗药物毒性剂量的能力。MDR活性还与阳离子亲脂性化合物（如荧光染料罗丹明123）的外排有关。最近有报道称正常淋巴细胞会排出罗丹明123，这表明这些细胞由于mdr1的表达而具有类似MDR的活性。在本研究中，我们使用双色流式细胞术分析观察到，在人淋巴细胞亚群中，排出罗丹明123的能力是异质性的，顺序为CD8大于CD4大于CD20。淋巴细胞中罗丹明123的外排和积累对已知的MDR逆转剂维拉帕米和聚乙二醇单硬脂酸酯HS 15敏感。总的来说，这些数据表明正常淋巴细胞中存在类似MDR的转运系统，这可能对参与淋巴细胞功能的分子的运输很重要。
