Abstract:
:The regulation of plasmin generation on cell surfaces is of critical importance in the control of vascular homeostasis. Cell-derived microparticles participate in the dissemination of biological activities. However, their capacity to promote plasmin generation has not been documented. In this study, we show that endothelial microparticles (EMPs) from tumor necrosis factor alpha (TNFalpha)-stimulated endothelial cells served as a surface for the generation of plasmin. The generation of plasmin involved expression of urokinase-type plasminogen activator (uPA) and its receptor (uPAR) at the surface of EMPs and was further increased by their ability to bind exogenous uPA on uPAR. Plasminogen was activated at the surface of EMPs in a dose-dependent, saturable, and specific manner as indicated by the inhibition of plasmin formation by epsilon-amino-caproic acid (epsilon-ACA) and carboxypeptidase B. EMP-induced plasmin generation affects tube formation mediated by endothelial progenitor cells. However, low amounts of EMPs increased tube formation, whereas higher concentrations inhibited it. Prevention of these effects by inhibitors of either uPA or plasmin underscore the key role of EMP-induced plasmin generation. In conclusion, we demonstrated that EMPs act as vectors supporting efficient plasmin generation and dissemination, a new pathway in the regulation of endothelial proteolytic activities with potential involvement in inflammation, angiogenesis, and atherosclerosis.
journal_name
Bloodjournal_title
Bloodauthors
Lacroix R,Sabatier F,Mialhe A,Basire A,Pannell R,Borghi H,Robert S,Lamy E,Plawinski L,Camoin-Jau L,Gurewich V,Angles-Cano E,Dignat-George Fdoi
10.1182/blood-2007-02-069997subject
Has Abstractpub_date
2007-10-01 00:00:00pages
2432-9issue
7eissn
0006-4971issn
1528-0020pii
blood-2007-02-069997journal_volume
110pub_type
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