Dear Editor:Growing evidence demonstrates that β 2 -glycoprotein I (β 2 GPI) is the key target for antiphospholipid antibodies which are closely associated with thrombotic events in antiphospholipid syndrome (APS) [1]. Anti-β 2 GPI/β 2 GPI complex can bind to the surface membrane of monocytes and endothelial cells, promoting tissue factor (TF) activity on these cells, and thus increasing the risk of thrombosis. However, the mechanisms underlying the actions of anti-β 2 GPI/β 2 GPI are not well understood. It was proposed that the effects of anti-β 2 GPI/β 2 GPI require the transduction of a signal into the cell and, therefore, involve a cell surface receptor. Since the effects of anti-β 2 GPI/β 2 GPI do not appear to be mediated by Fc receptors, nor by negatively-charged phospholipids of the cell membrane, investigators posit the existence of a distinct cell surface receptor for β 2 GPI.In previous work, McCrae and colleagues demonstrated annexin A2 (ANX2, formerly called annexin II) as a highaffinity receptor for β 2 GPI on endothelial cells (Ma et al) [2]. Furthermore, they showed that ANX2 mediates anti-β 2 GPI/β 2 GPI complex binding to endothelial cell surface, stimulating the activation of endothelium and increasing the levels of TF, VCAM-1 (vascular cell adhesion molecule 1) and other inflammatory molecules in circulation [3]. Their findings establish an important point that a cell surface receptor is critical in mediating the effects of autoantiphospholipid antibodies (APL) on endothelial cells. Our previous study showed that anti-β 2 GPI could induce monocyte TF activity in APS [4]. Finding the mediator for anti-β 2 GPI/β 2 GPI in monocytes would be a key step in further understanding APL associated pathology in APS.McCrae's observation on endothelial cells led us to ask similar questions for monocytes. Is ANX2 expressed on monocytes? Does ANX2 mediate anti-β 2 GPI/β 2 GPI binding to monocytes, leading to stimulation of TF expression?Using the specific anti-ANX2 antibody, we have demonstrated by western blotting that both peripheral blood monocytes and the monocytic cell line, MM6 cells, contained ANX2 protein (36 kDa) in their membrane lysates ( Figure 1A). The surface ANX2 expression on blood monocytes ( Figure 1B a-c) and MM6 cells ( Figure 1B d-f) was also detected by flow cytometry analysis. The mean fluorescence intensity of cells treated with the calcium chelator EGTA was obviously weaker than that of cells without the EGTA treatment, suggesting that ANX2 is a calcium-dependent protein, which is consistent with previously published results [5].We next investigated whether ANX2 can mediate anti-β 2 GPI/β 2 GPI binding to monocytes, and thus stimulating TF expression on these cells. The results showed that TF activity on monocytes induced by anti-β 2 GPI/β 2 GPI was decreased when cells were pre-incubated with the monoclonal anti-ANX2 antibody, while the control antibody had no such inhibitory effects. Importantly, anti-ANX2 antibody did not affect the effect of LPS on TF expression ( Figure 1C)....