Interaction of endothelial microparticles with monocytic cells in vitro induces tissue factor–dependent procoagulant activity

F Sabatier, V Roux, F Anfosso, L Camoin… - Blood, The Journal …, 2002 - ashpublications.org
F Sabatier, V Roux, F Anfosso, L Camoin, J Sampol, F Dignat-George
Blood, The Journal of the American Society of Hematology, 2002ashpublications.org
In the present study we investigated whether endothelial microparticles (EMPs) can bind to
monocytic THP-1 cells and modulate their procoagulant properties. Using flow cytometry, we
demonstrated that EMPs express adhesive receptors similar to those expressed by activated
endothelial cells. Expression of endothelial antigens by THP-1 cells incubated with EMP
was shown by immunoperoxidase staining and flow cytometry using antibodies directed
against E-selectin, VCAM-1, and endoglin. EMP binding to THP-1 cells was time-and …
In the present study we investigated whether endothelial microparticles (EMPs) can bind to monocytic THP-1 cells and modulate their procoagulant properties. Using flow cytometry, we demonstrated that EMPs express adhesive receptors similar to those expressed by activated endothelial cells. Expression of endothelial antigens by THP-1 cells incubated with EMP was shown by immunoperoxidase staining and flow cytometry using antibodies directed against E-selectin, VCAM-1, and endoglin. EMP binding to THP-1 cells was time- and concentration- dependent, reached a plateau at 15 minutes, and had an EMP-to-monocyte ratio of 50:1. EMP binding was not affected by low temperature and was not followed by the restoration of phosphatidylserine asymmetry, suggesting that adhesion was not followed by fusion. A 4-hour incubation of THP-1 cells with EMP led to an increase in procoagulant activity as measured by clotting assay. Concomitantly, THP-1 exhibited increased levels of tissue factor (TF) antigen and TF mRNA compared to control cells. The ability of EMP to induce THP-1 procoagulant activity was significantly reduced when THP-1 cells were incubated with EMP in the presence of blocking antibodies against ICAM-1 and β2 integrins. These results demonstrate that EMPs interact with THP-1 cells in vitro and stimulate TF-mediated procoagulant activity that is partially dependent on the interaction of ICAM-1 on EMP and its counterreceptor, β2 integrins, on THP-1 cells. Induction of procoagulant activity was also demonstrated using human monocytes, suggesting a novel mechanism by which EMP may participate in the dissemination and amplification of procoagulant cellular responses.
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