ABSTRACT: Background. We recently assigned a new fibrinolytic function to cell-derived microparticles in vitro. The relevance of this novel property of microparticles to the in vivo situation was explored in these studies.Design and Methods. Circulating microparticles were isolated from plasma of thrombotic thrombocytopenic purpura, systemic lupus erythematosus or cardiovascular disease patients and from healthy subjects. Microparticles were also obtained from purified human blood cell subpopulations. Identification of plasminogen activators on microparticles was performed by flow cytometry and ELISA, their capacity to generate plasmin quantified with a chromogenic assay and their fibrinolytic activity by zymography.Results. Circulating microparticles isolated from patients generate a range of plasmin activity at their surface. This property was related to a variable content in uPA and/or tPA. Using distinct microparticle subpopulations, we demonstrate that plasmin is generated on endothelial and leukocyte microparticles, but is absent on microparticles from platelet or erythrocyte origin. Leukocyte-derived microparticles bear uPA and its receptor uPAR whereas endothelial microparticles carry tPA and tPA/inhibitor complexes. Conclusions. Endothelial and leukocyte microparticles, bearing respectively tPA or uPA, support a part of the fibrinolytic activity in the circulation that is modulated in pathological settings. This blood-borne fibrinolytic activity conveyed by microparticles provides a more comprehensive view on the role of microparticles in the hemostatic equilibrium.
Haematologica 06/2012; · 6.42 Impact Factor