白血病细胞系纤溶活性及全反式维甲酸对其影响  

The fibrinolytic activity in leukemic cell lines and its alteration on all-trans retinoic acid treatment

作　　者：谢燕[1] 王兆钺[1] 张威[1] 戴兰[1] 白霞[1] 

机构地区：[1]苏州大学附属第一医院,江苏省血液研究所215006

出　　处：《中华血液学杂志》2006年第9期588-592,共5页Chinese Journal of Hematology

基　　金：江苏省卫生厅科技基金会重点科研课题资助项目(K200401)

摘　　要：目的研究不同白血病细胞系的纤溶活性,观察在全反式维甲酸(ATRA)作用下白血病细胞纤溶活性的变化及对尿激酶型纤溶酶原激活剂受体(uPAR)和膜联蛋白Ⅱ(AnnexinⅡ)表达的影响。方法用发色底物法测定白血病细胞系 NB4、SHI-1、K562、Jurkat、Raji 细胞的纤溶活性。用流式细胞术检测上述细胞表而 uPAR 和 AnnexinⅡ的表达,以 RT-PCR 方法检测 uPAR mRNA 和 AnnexinⅡmRNA 的表达。结果 NB4细胞和 SHI-1细胞与纤溶酶原作用后上清液纤溶酶活性明显升高,ATRA 处理后的 NB4细胞纤溶活性明显下降。uPAR 单抗可使 SHI-1细胞和 NB4细胞的纤溶活性明显下降。SHI-1细胞与 NB4细胞表面的 uPAR 和 AnnexinⅡ及其相应的 mRNA 表达较高,ATRA 能下调NB4细胞 AnnexinⅡ和 uPAR 及其相应的 mRNA 表达。结论不同白血病细胞使纤溶酶原转化为纤溶酶的能力不同,其中 SHI-1细胞和 NB4细胞促纤溶活性较强。白血病细胞表面 AnnexinⅡ和 uPAR 共同参与了促纤溶作用。ATRA 主要通过下调 NB4细胞的 AnnexinⅡ和 uPAR 蛋白及其 mRNA 的表达,纠正早幼粒细胞白血病的高纤溶状态。Objectives To study the fibrinolytic activity and the expression of uPAR and Annexin Ⅱ in leukemic cell lines and their alterations on all-trans retinoic acid （ATRA） treatment. Methods The fibrinolytic activity was measured by chromogenic assay in NB4, SHI-1, K562, Jurkat and Raji cell lines. The protein expression of uPAR and Annexin Ⅱ on cells surface and the mRNA expression of uPAR and Annexin Ⅱ in cells of these cell lines were detected using flow cytometry and RT-PCR method respectively. Results The plasmin activity in supernatant was increased significantly after incubation of SHI-1 and NB4 cells with plasminogen. The plasmin activity of NB4 cells was obviously decreased by ATRA. The plasmin activity of NB4 and SHI-1 cells was significantly decreased by uPAR monoclonal antibodies. The expressions of uPAR and Annexin Ⅱ and their mRNA in SHI-1 and NB4 cells were higher than that in other cell lines. ATRA could remarkablly decrease the expressions of Annexin Ⅱ and uPAR and their mRNA in NB4 cells. Conclusion In leukemia cell lines, NB4 and SHI-1 cells have stronger fibrinolytic activity. Both Annexin Ⅱ and uPAR on the leukemic cell membranes might contribute to this activity. The high fibrinolytic activity can be corrected by ATRA by down-regulating Annexin Ⅱ and uPAR mRNA and protein expression in NB4 cells.

关 键 词：细胞 白血病 受体 尿激酶 膜联蛋白Ⅱ 基因表达 维甲酸 

分 类 号：R733.7[医药卫生—肿瘤]