Platelet Associated u-PA Up-regulates u-PA Synthesis by Endothelial Cells

L. Camoin-Jau; R. Pannell; F Anfosso; N. Bardin; F. Sabatier; J. Sampol; V. Gurewich; F. Dignat-George

doi:10.1055/s-0037-1613246

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2002; 88(03): 517-523
DOI: 10.1055/s-0037-1613246

Review Article

Schattauer GmbH

Platelet Associated u-PA Up-regulates u-PA Synthesis by Endothelial Cells

Authors

L. Camoin-Jau

¹INSERM EMI 00-19, Laboratoire d’Hématologie, Univ Méditerra née, UFR de Pharmacie and Hôpital de la Conception, Marseille, France
R. Pannell

²Vascular Research Laboratory, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
F Anfosso

¹INSERM EMI 00-19, Laboratoire d’Hématologie, Univ Méditerra née, UFR de Pharmacie and Hôpital de la Conception, Marseille, France
N. Bardin

¹INSERM EMI 00-19, Laboratoire d’Hématologie, Univ Méditerra née, UFR de Pharmacie and Hôpital de la Conception, Marseille, France
F. Sabatier

¹INSERM EMI 00-19, Laboratoire d’Hématologie, Univ Méditerra née, UFR de Pharmacie and Hôpital de la Conception, Marseille, France
J. Sampol

¹INSERM EMI 00-19, Laboratoire d’Hématologie, Univ Méditerra née, UFR de Pharmacie and Hôpital de la Conception, Marseille, France
V. Gurewich

²Vascular Research Laboratory, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
F. Dignat-George

¹INSERM EMI 00-19, Laboratoire d’Hématologie, Univ Méditerra née, UFR de Pharmacie and Hôpital de la Conception, Marseille, France

Abstract

Summary

Adhesion of platelets to endothelium has been shown to induce important changes in endothelial properties. In this study, we examined the effect of platelet-endothelial cell interactions on the expression of urokinase-type plasminogen activator (u-PA) by human microvascular endothelial cells. After incubation of endothelial cells with platelets, a dose-dependent increase in the expression of u-PA Ag was observed and reached a plateau for a ratio of 300 platelets per endothelial cells. The u-PA Ag upregulation resulted from an increase in u-PA mRNA that originated from a synthesis by endothelial cells since no u-PA mRNA was detected in platelets. The platelet-induced u-PA synthesis was inhibited when the endothelial cells were pre-treated with phospholipase C to remove the u-PA receptor, or when the platelets were incubated with an antibody that blocks the binding of u-PA to u-PAR. Taken together, these data indicate that u-PA present on the platelet surface interacts with u-PAR on the endothelial cells and induces the u-PA synthesis. This mechanism may represent a physiological control of platelet-mediated intravascular fibrin deposition.

Keywords

Urokinase - platelets - endothelial cells - urokinase-plasminogen receptor

Full Text

References

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