C0082 Circulating leukocyte- and endothelial-derived microparticles support a fibrinolytic activity

peer reviewedBackground: Microparticles (MPs) derived from activated platelets, leukocytes and endothelial cells are well known for their procoagulant activity. We recently assigned a new fibrinolytic function to endothelial derived MPs in vitro. However, the relevance of this novel propertyto the in vivo situation remains unclear. Methods: Circulating MPs were isolated from plasma of thrombotic thrombocytopenic purpura or cardiovascular disease patients and from healthy subjects. MPswere also obtained from purified human blood cell subpopulations. Identification of plasminogen activators on MPs was performed by zymography and their capacity to generate plasmin by chromogenic assay. Results: Circulating MPs isolated from patientsgenerate a range of plasmin activity at their surface. This property was related to a variable content in uPA and/or tPA. Using distinct MP subpopulations derived from endothelial cells, platelets, leukocytes and erythrocytes, we demonstrated that plasmin is generated on endothelial- and leukocytederived MPs, but is absent on MPs from platelet or erythrocyte origins. Leukocyte-derived MPs bear uPA and its receptor uPAR whereas endothelial-derived MPs carry tPA and tPA/inhibitor complexes. Comment: Endothelial- and leukocyte-derived MPs, bearing respectively tPA or uPA, support at least a part of fibrinolytic activity in the circulation that is modulated in pathological settings. This blood-borne fibrinolytic activity conveyed by MPs provides a more comprehensive view on the role of MPs in the haemostatic equilibrium and put forward the basis for a potential new biomarker