Annexin A2 mediates anti-beta 2 GPI/beta 2 GPI-induced tissue factor expression on monocytes.

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.