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Published on: October 31, 2016
Platelet associated u-PA up-regulates u-PA synthesis by endothelial cells
L Camoin-Jau1, R Pannell, F Anfosso
1INSERM EMI 00-19, Laboratoire d'Hematologie, Univ Mediterranée, UFR de Pharmacie and Hĵpital de la Conception, Marseille, France.
Platelet interaction with endothelial cells increases urokinase-type plasminogen activator (u-PA) expression. This platelet-induced u-PA synthesis is mediated by platelet u-PA binding to endothelial cell u-PAR.
Area of Science:
- Endothelial cell biology
- Hematology
- Molecular biology
Background:
- Platelet adhesion to endothelium alters endothelial cell properties.
- Urokinase-type plasminogen activator (u-PA) plays a role in fibrinolysis and extracellular matrix remodeling.
Purpose of the Study:
- To investigate the effect of platelet-endothelial cell interactions on u-PA expression in human microvascular endothelial cells.
- To elucidate the mechanism by which platelets influence u-PA synthesis.
Main Methods:
- Incubation of human microvascular endothelial cells with varying ratios of platelets.
- Measurement of u-PA antigen (Ag) and mRNA expression.
- Inhibition studies using phospholipase C and anti-u-PA antibodies.
Main Results:
- Platelet incubation led to a dose-dependent increase in u-PA Ag expression, plateauing at 300 platelets/endothelial cell.
- Upregulation of u-PA Ag resulted from increased endothelial cell u-PA mRNA synthesis.
- Platelet-induced u-PA synthesis was inhibited by phospholipase C treatment or blocking antibodies against u-PA/u-PAR interaction.
Conclusions:
- Platelet surface u-PA interacts with endothelial cell urokinase plasminogen activator receptor (u-PAR) to induce endothelial u-PA synthesis.
- This interaction represents a potential physiological mechanism for controlling platelet-mediated intravascular fibrin deposition.
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