Fibrinolytic cross-talk: a new mechanism for plasmin formation
| Autor: | Romaric Lacroix, Tiphaine Dejouvencel, Laurent Plawinski, H. Roger Lijnen, Loïc Doeuvre, Eduardo Anglés-Cano, Françoise Dignat-George |
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| Přispěvatelé: | 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, 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) |
| Rok vydání: | 2010 |
| Předmět: |
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 |
| Zdroj: | Blood Blood, 2010, 115 (10), pp.2048-56. ⟨10.1182/blood-2009-06-228817⟩ Blood; Vol 115 Blood, American Society of Hematology, 2010, 115 (10), pp.2048-56. ⟨10.1182/blood-2009-06-228817⟩ |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood-2009-06-228817 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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