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Blood, 1 June 2002, Vol. 99, No. 11, pp. 3962-3970
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Interaction of endothelial microparticles with monocytic cells in
vitro induces tissue factor-dependent procoagulant
activity
Florence Sabatier,
Veronique Roux,
Francine Anfosso,
Laurence Camoin,
José Sampol, and
Françoise Dignat-George
From INSERM EMI 00-19, Laboratoire d'Hématologie
et d'Immunologie, UFR de Pharmacie, Université de la
Méditerranée, Marseilles, and Laboratoire
d'Hématologie, Centre Hospitalier Universitaire La Conception,
Marseilles, France.
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  2 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, 2 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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