Zhou Hong, Wang Haibo, Li Na, Yu Ying, Huang Hongliang, Yan Yihong, Wang Ting
Department of Clinical Laboratory and Hematology, Jiangsu University, Jiangsu 212013, PR China.
Int J Mol Med. 2009 Oct;24(4):557-62. doi: 10.3892/ijmm_00000265.
Growing evidence suggests that autoantibodies directly contribute to hypercoagulability in the antiphospholipid syndrome (APS). One proposed mechanism is the antibody-induced expression of tissue factor (TF) by blood monocytes. Annexin A2 (ANX2), a mediator of cell surface-specific plasmin generation, was identified to mediate endothelial cell activation by anti-beta2-glycoprotein I (anti-beta 2 GPI) antibody. Our previous study suggested that ANX2 was also involved in anti-beta 2 GPI/beta 2 GPI-induced TF expression on monocytes. In the current study, it was further demonstrated that beta 2 GPI interacts with ANX2 not only in a cell-dependent form but also in a cell-free system. To further confirm the effects of ANX2 on anti-beta 2 GPI/beta 2 GPI-induced TF expression, an ANX2 cDNA-containing vector was transfected into HEK 293T cells which had originally little ANX2, then cells were treated by anti-beta 2 GPI/beta 2 GPI complex. It was found that transfected HEK 293T cells could express more TF both at mRNA and protein levels than that of no-transfected cells. On the other hand, the TF expression was dramatically decreased in the THP-1 cells in which the ANX2 RNA interference was performed. In conclusion, these results indicate that ANX2 on cell surface functions as a mediator boosting TF expression on monocytes induced by anti-beta 2 GPI/beta 2 GPI complex, which is contributed to the thrombotic events in APS.
越来越多的证据表明，自身抗体直接导致抗磷脂综合征（APS）中的高凝状态。一种提出的机制是抗体诱导血液单核细胞表达组织因子（TF）。膜联蛋白A2（ANX2）是细胞表面特异性纤溶酶生成的介质，已被确定可介导抗β2糖蛋白I（抗β2GPI）抗体诱导的内皮细胞活化。我们之前的研究表明，ANX2也参与抗β2GPI/β2GPI诱导的单核细胞TF表达。在本研究中，进一步证明β2GPI不仅以细胞依赖的形式与ANX2相互作用，而且在无细胞系统中也相互作用。为了进一步证实ANX2对抗β2GPI/β2GPI诱导的TF表达的影响，将含有ANX2 cDNA的载体转染到原本几乎没有ANX2的HEK 293T细胞中，然后用抗β2GPI/β2GPI复合物处理细胞。发现转染的HEK 293T细胞在mRNA和蛋白质水平上比未转染的细胞表达更多的TF。另一方面，在进行了ANX2 RNA干扰的THP-1细胞中，TF表达显著降低。总之，这些结果表明，细胞表面的ANX2作为一种介质，促进抗β2GPI/β2GPI复合物诱导的单核细胞TF表达，这与APS中的血栓形成事件有关。
