人单核细胞上尿激酶型纤溶酶原激活物受体参与细胞迁移
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Urokinase-type Plasminogen Activator Receptor Expression in Monocytes Mediates Cell Migration
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    目的研究单核细胞膜蛋白-尿激酶型纤溶酶原激活物受体在细胞迁移过程中的作用及相关机制。方法采用密度梯度离心和粘附法分离、纯化人外周血单核细胞;在单核细胞趋化蛋白1诱导下,观察尿激酶型纤溶酶原激活物及其抗体、纤溶酶原激活物抑制剂1和尿激酶型纤溶酶原激活物受体抗体等因子对单核细胞迁移的影响。结果在25μg/L单核细胞趋化蛋白1诱导下,尿激酶型纤溶酶原激活物有促进单核细胞迁移的倾向,迁移细胞由对照组的179.40±38.49升高至251.00±26.11,P=0.076;尿激酶型纤溶酶原激活物抗体和纤溶酶原激活物抑制剂1对细胞迁移没有明显影响;而尿激酶型纤溶酶原激活物氨基末端则抑制迁移的细胞数至56.40±76.98,与对照组比较,差异有显著性(p<0.01)。加入抗尿激酶型纤溶酶原激活物受体抗体之后单核细胞迁移也受到抑制,160μg/L组迁移细胞数为151.20±20.33,与10μg/L组(228.40±83.96)比较显著降低(p<0.05)。结论尿激酶型纤溶酶原激活物受体参与单核细胞趋化蛋白1诱导的单核细胞迁移,尿激酶型纤溶酶原激活物氨基末端对迁移具抑制作用,该作用甚至强于尿激酶型纤溶酶原激活物受体抗体,提示单核细胞迁移中尿激酶型纤溶酶原激活物及其受体分子间相互作用的重要性。

    Abstract:

    Aim To examine the roles of urokinase-type plasminogen activator receptor(uPAR),a cellular receptor for the urokinase-type plasminogen activator(uPA) in monocytic migration induced by Monocyte chemotactic protein-1(MCP-1). Methods Monocytes were separated and purified by density gradient centrifugation and adhering assay.MCP-1 were added into each lower chamber of TranswellR at a concentration of 25 μg/L.In the upper chamber,monocytes were incubated with uPA antibody,uPAR antibody,uPA and Plasminogen Activator Inhibitor(PAI-1) respectively,the number of monocytes moved through TranswellR mambrane were calculated to detect their effect on cell migration. Results uPA had a trend to promote monocytic migration,the number of migrated cells was increased from 179.40±38.49 of the control to 251.00±26.11,P=0.076.PAI-1 and uPA antibody had no effect on cell migration,however the amino terminal fragment of uPA(ATF)significantly suppressed the cells to migrate through transwell,from 179.40±38.49 of the control to 56.40±76.98,p<0.05.Similar result was observed in uPAR antibody,the number of migrated monocytes was decreased from 228.40±83.96 to 151.20±20.33,when the concentration of uPAR rised from 10 μg/L to 160 μg/L,p<0.05. Conclusions uPAR,a membrane protein,participated in monocytic migration induced by MCP-1.The suppressive effect of ATF,which was stronger than that of anti-uPAR antibody,indicated that a specific uPA-uPAR interaction may play an important role in monocytic migration.

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陈未,朱文玲,方全,陈连凤,张抒扬,陈太波,刘震宇,谢洪智.人单核细胞上尿激酶型纤溶酶原激活物受体参与细胞迁移[J].中国动脉硬化杂志,2007,15(8):613~617.

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  • 收稿日期:2007-05-26
  • 最后修改日期:2007-07-16
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