Platelets docking to VWF prevent leaks during leukocyte extravasation by stimulating Tie-2.
| Autor: | Braun LJ; Max Planck Institute for Molecular Biomedicine, Münster, Germany., Stegmeyer RI; Max Planck Institute for Molecular Biomedicine, Münster, Germany., Schäfer K; Max Planck Institute for Molecular Biomedicine, Münster, Germany., Volkery S; Max Planck Institute for Molecular Biomedicine, Münster, Germany., Currie SM; Max Planck Institute for Molecular Biomedicine, Münster, Germany., Kempe B; Max Planck Institute for Molecular Biomedicine, Münster, Germany., Nottebaum AF; Max Planck Institute for Molecular Biomedicine, Münster, Germany., Vestweber D; Max Planck Institute for Molecular Biomedicine, Münster, Germany. |
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| Jazyk: | angličtina |
| Zdroj: | Blood [Blood] 2020 Jul 30; Vol. 136 (5), pp. 627-639. |
| DOI: | 10.1182/blood.2019003442 |
| Abstrakt: | Neutrophil extravasation requires opening of the endothelial barrier but does not necessarily cause plasma leakage. Leaks are prevented by contractile actin filaments surrounding the diapedesis pore, keeping this opening tightly closed around the transmigrating neutrophils. We have identified the receptor system that is responsible for this. We show that silencing, or gene inactivation, of endothelial Tie-2 results in leak formation in postcapillary venules of the inflamed cremaster muscle at sites of neutrophil extravasation, as visualized by fluorescent microspheres. Leakage was dependent on neutrophil extravasation, because it was absent upon neutrophil depletion. We identified the Cdc42 GTPase exchange factor FGD5 as a downstream target of Tie-2 that is essential for leakage prevention during neutrophil extravasation. Looking for the Tie-2 agonist and its source, we found that platelet-derived angiopoietin-1 (Angpt1) was required to prevent neutrophil-induced leaks. Intriguingly, blocking von Willebrand factor (VWF) resulted in vascular leaks during transmigration, indicating that platelets interacting with endothelial VWF activate Tie-2 by secreting Angpt1, thereby preventing diapedesis-induced leakiness. (© 2020 by The American Society of Hematology.) |
| Databáze: | MEDLINE |
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