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.
Zhou
Hong
H
Department of Clinical Laboratory and Hematology, Jiangsu University, Jiangsu 212013, PR China. hongzhou@ujs.edu.cn
Wang
Haibo
H
Li
Na
N
Yu
Ying
Y
Huang
Hongliang
H
Yan
Yihong
Y
Wang
Ting
T
D017306:Annexin A2 / Q000235:genetics / Q000502:physiology*; D000936:Antigen-Antibody Complex / Q000494:pharmacology*; D002460:Cell Line; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism*; D013925:Thromboplastin / Q000235:genetics / Q000378:metabolism*; D053482:beta 2-Glycoprotein I / Q000276:immunology* / Q000378:metabolism*
D017306:Annexin A2; D000936:Antigen-Antibody Complex; D053482:beta 2-Glycoprotein I; D013925:Thromboplastin