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Blood, 1 October 2007, Vol. 110, No. 7, pp. 2432-2439. Prepublished online as a Blood First Edition Paper on July 2, 2007; DOI 10.1182/blood-2007-02-069997. This Article Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2007-02-069997v1 110/7/2432    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Lacroix, R. Articles by Dignat-George, F. Search for Related Content PubMed PubMed Citation Articles by Lacroix, R. Articles by Dignat-George, F. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 1, 2007 Accepted June 22, 2007 Activation of plasminogen into plasmin at the surface of endothelial microparticles: a mechanism that modulates angiogenic properties of endothelial progenitor cells in vitro Romaric Lacroix, Florence Sabatier, Agnes Mialhe, Agnes Basire, Ralph Pannell, Helene Borghi, Stephane Robert, Edouard Lamy, Laurent Plawinski, Laurence Camoin-Jau, Victor Gurewich, Eduardo Angles-Cano, and Francoise Dignat-George* UMR-S U608 INSERM, UFR de Pharmacie, Universite de la Mediterranee, Marseille, France Vascular Research Laboratory, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States Service de Microscopie Electronique, UFR de Medecine, Universite de la Mediterranee, Marseille, France Inserm Cyceron, Universite de Caen, Caen, France * Corresponding author; email: dignat{at}pharmacie.univ-mrs.fr. 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 (EMP) from TNF-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 EMP and was further increased by their ability to bind exogenous uPA on uPAR. Plasminogen was activated at the surface of EMP in a dose-dependent, saturable and specific manner as indicated by the inhibition of plasmin formation by -amino-caproic acid (-ACA) and carboxypeptidase B. EMP-induced plasmin generation affects tube formation mediated by endothelial progenitor cells. However, low amounts of EMP 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 EMP 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: It's not size, it's substance Edward F. Plow and Elzbieta Pluskota Blood 2007 110: 2224-2225. [Full Text] [PDF]

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