IL-6受体在人白血病细胞膜上的表达及亲和力

Density and Affinity of IL-6 Receptors in Human Leukemic Cells

目的 :研究各种白血病细胞膜IL 6R的表达、密度及亲和力 ,为深入探讨对IL 6 /IL 6R系统介导IL 6 PE40外毒素融合蛋白靶向杀伤白血病细胞的敏感性提供可靠依据。方法 :采用放射性配基结合实验 (RBA)并结合Scatchard作图法 ,系统分析IL 6R在 8种极具代表性的人类白血病细胞系U937,HL 6 0 ,KG1,TF1,K5 6 2 ,CEM ,HuT2 8和Raji上的表达密度及亲和力 ,同时应用流式细胞术 (FACS)检测IL 6R的α和 β亚单位蛋白在这些白血病细胞上的表达。结果 :RBA表明 ,粒、单、红白血病细胞系HL 6 0 ,U937,KG1和TF1表面存在着高亲和力IL 6R ,平均IL 6R密度 /细胞分别为 2 5 0 2个 ,2 874个 ,2 319个及 932 9个 ,而淋系白血病细胞系CEM ,HuT2 8和Raji以及慢粒K5 6 2细胞系则未测到IL 6R。FACS显示 ,HL 6 0 ,KG1,U937和TF1均高表达IL 6R的α亚单位蛋白 ,而CEM ,HuT2 8及K5 6 2则不表达IL 6Rα亚单位蛋白 ;IL 6Rβ亚单位蛋白在U937,KG1,TF1,HuT2 8及CEM中呈阳性表达 ,而在HL 6 0 ,Raji和K5 6 2细胞中则为阴性。结论 :鉴于粒、单、红白血病细胞异常高表达IL 6R ,而淋系和慢粒白血病呈阴性表达这一事实 ,提示急非淋白血病可能更适合用重组IL 6 PE40外毒素融合蛋白进行IL 6 /IL 6R介导的靶向治疗。

Objective: To make a study of density and affinity of IL 6R in human leukemic cell lines, and discuss the affection of high affinity IL 6R to the targeted treatment of leukemia with IL 6 PE40 fusion protein. Methods: Radial binding assay with scatchard plot and FACS were used to analysis the density and affinity of IL 6R and protein expression of IL 6Rα and β subunits in totally 8 representative human leukemic cell lines. Results: Myelocytic, monocytic and erythrocytic leukemic cell lines U937, HL 60, KG1 and TF1 express high affinity IL 6R, whose average density per cell is 2 502, 2 874, 2 319 and 9 329 respectively, however no 125 I IL 6 binding was detected on chronic myelocytic leukemic cell line K562 and lymphoblastic leukemic cell lines such as Raji, CEM and HuT28. These results correlate with those of FACS highly. Conclusion:These observations suggest that acute nonlymphoblastic leukemic cells may be more suitable for targeted treatment with IL 6 PE40 fusion protein.