1. Fibrinolytic cross-talk: a new mechanism for plasmin formation
- Author
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Romaric Lacroix, Tiphaine Dejouvencel, Laurent Plawinski, H. Roger Lijnen, Loïc Doeuvre, Eduardo Anglés-Cano, Françoise Dignat-George, Hémostase, bio-ingénierie et remodelage cardiovasculaires (LBPC), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut Galilée-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sérine protéases et physiopathologie de l'unité neurovasculaire, Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie de l'Endothelium, Vascular research center of Marseille (VRCM), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre-Imagerie, Neurosciences, et Application aux Pathologies (CI-NAPS - UMR 6232), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Center for Molecular and Vascular Biology, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Inserm European Community's Seventh Framework Programme (FP7/2007-2013) Excellentie financiering, KU Leuven Lower-Normandy Regional Council, European Project: 201024,EC:FP7:HEALTH,FP7-HEALTH-2007-A,ARISE(2008), Université Paris Diderot - Paris 7 (UPD7)-Université Paris 13 (UP13)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Galilée, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)
- Subjects
MESH: Signal Transduction ,Plasmin ,medicine.medical_treatment ,MESH: Antifibrinolytic Agents ,urokinase ,Cell Communication ,MESH: Fibrinolysin ,030204 cardiovascular system & hematology ,Biochemistry ,MESH: Fibrinolysis ,Mice ,0302 clinical medicine ,Antifibrinolytic agent ,MESH: Plasminogen ,MESH: Animals ,Fibrinolysin ,Cells, Cultured ,0303 health sciences ,biology ,medicine.diagnostic_test ,Chemistry ,Fibrinolysis ,MESH: Plasminogen Activators ,lysine-binding site ,Hematology ,Antifibrinolytic Agents ,Extracellular Matrix ,Cell biology ,Aminocaproic Acid ,platelets ,plasminogen ,monocytes ,Signal Transduction ,MESH: Cells, Cultured ,medicine.drug ,Proteolysis ,MESH: Receptor Cross-Talk ,Immunology ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,MESH: Extracellular Matrix ,endothelial microparticles ,Article ,MESH: Urokinase-Type Plasminogen Activator ,Plasminogen Activators ,03 medical and health sciences ,MESH: 6-Aminocaproic Acid ,MESH: Cell Communication ,medicine ,Animals ,Humans ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,MESH: Mice ,030304 developmental biology ,Urokinase ,MESH: Humans ,Activator (genetics) ,Receptor Cross-Talk ,Cell Biology ,Urokinase-Type Plasminogen Activator ,Fibronectin ,MESH: Protein Processing, Post-Translational ,biology.protein ,Protein Processing, Post-Translational ,Plasminogen activator - Abstract
Fibrinolysis and pericellular proteolysis depend on molecular coassembly of plasminogen and its activator on cell, fibrin, or matrix surfaces. We report here the existence of a fibrinolytic cross-talk mechanism bypassing the requirement for their molecular coassembly on the same surface. First, we demonstrate that, despite impaired binding of Glu-plasminogen to the cell membrane by ϵ-aminocaproic acid (ϵ-ACA) or by a lysine-binding site–specific mAb, plasmin is unexpectedly formed by cell-associated urokinase (uPA). Second, we show that Glu-plasminogen bound to carboxy-terminal lysine residues in platelets, fibrin, or extracellular matrix components (fibronectin, laminin) is transformed into plasmin by uPA expressed on monocytes or endothelial cell–derived microparticles but not by tissue-type plasminogen activator (tPA) expressed on neurons. A 2-fold increase in plasmin formation was observed over activation on the same surface. Altogether, these data indicate that cellular uPA but not tPA expressed by distinct cells is specifically involved in the recognition of conformational changes and activation of Glu-plasminogen bound to other biologic surfaces via a lysine-dependent mechanism. This uPA-driven cross-talk mechanism generates plasmin in situ with a high efficiency, thus highlighting its potential physiologic relevance in fibrinolysis and matrix proteolysis induced by inflammatory cells or cell-derived microparticles.
- Published
- 2010
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