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

Abstract

SummaryAdhesion 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.

High urokinase expression contributes to the angiogenic properties of endothelial cells derived from circulating progenitors

“…2A, B). In ordertoinvestigatewhethermembrane uPAwas only bound to uPAR, uPAand uPAR expression levels were measured after incubation of adherentcells with PI-PLC, a condition previously shown to remove uPAR from cell surface (20). After PI-PLC treatment of both HUVECa nd EPDC, the membrane expression of uPAw as undetectable while,a se xpected,the expression levelofuPA Rwas reduced by 80% compared to untreatedcells (datanot shown),suggesting that membrane uPAwas exclusivelybound to GPI-anchored molecules.…”

“…Similar labelling and flowc ytometry protocol wasu sedf or phenotypic analysis of EPDC, using the following primarymonoclonalantibodies: KDR (clone KDR-1, Sigma),C D146 (cloneS endo-1, Biocytex, Marseille,F rance), CD144, CD34 (clone 581), PECAM-1( CD31,c lone 1F11), CD45 (clone J.33) and CD14 (clone RM052) from Beckman Coulter Immunotech. In some experiments flowc ytometry measurement of uPAand uPAR expression levelwas performed after incubation of adherentcells with 0.9 U/ml of phospholipase Cphosphatidylinositol-specific (PI-PLC,Sigma)for 1h at 37°C, as previously described (20).…”

Activated platelets increase fibrinolysis of mesenchymal progenitor cells

“…10 In vitro studies indicate that activated platelets enhance fibrinolysis of endothelial cells. [11][12][13] Endothelial cells and mesenchymal cells are both key elements of the granulation tissue; however, the influence of platelets on mesenchymal progenitors has not been examined so far. 2,3 Mesenchymal progenitors are present in a broad spectrum of tissues, such as bone marrow, periosteum, synovial membrane, and the vasculature where they are supposed to contribute to bone remodeling and regeneration.…”

Role of Plasminogen Activation System in Platelet Pathophysiology: Emerging Concepts for Translational Applications

“…Another mechanism for uPA-mediated plasmin formation has been reported: glu-plasminogen bound to platelet surface was converted to plasmin with a high efficiency by uPA expressed on monocytes or endothelial cells-derived microparticles [ 45 ]. Importantly, uPA associated with platelet surface was able to upregulate uPA mRNA synthesis by endothelial cells [ 71 ]. Through this mechanism, platelets may control intravascular fibrin deposition.…”