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Fibrinolytic cross-talk: a new mechanism for plasmin formation.
- Source :
-
Blood [Blood] 2010 Mar 11; Vol. 115 (10), pp. 2048-56. Date of Electronic Publication: 2009 Dec 07. - Publication Year :
- 2010
-
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 epsilon-aminocaproic acid (epsilon-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.
- Subjects :
- Aminocaproic Acid pharmacology
Animals
Antifibrinolytic Agents pharmacology
Cell Communication physiology
Cells, Cultured
Extracellular Matrix drug effects
Extracellular Matrix metabolism
Fibrinolysis drug effects
Humans
Mice
Plasminogen metabolism
Plasminogen Activators metabolism
Protein Processing, Post-Translational
Receptor Cross-Talk drug effects
Receptor Cross-Talk physiology
Signal Transduction drug effects
Signal Transduction physiology
Urokinase-Type Plasminogen Activator metabolism
Fibrinolysin metabolism
Fibrinolysis physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1528-0020
- Volume :
- 115
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 19996088
- Full Text :
- https://doi.org/10.1182/blood-2009-06-228817