白血病细胞系纤溶活性及全反式维甲酸对其影响

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面uPAR和AnnexinⅡ的表达，以RT—PCR方法检测uPARmRNA和AnnexinⅡ mRNA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。

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

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 remarkably 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 I and uPAR mRNA and protein expression in NB4 cells.