Peptide Bbeta(15-42) preserves endothelial barrier function in shock

  • Loss of vascular barrier function causes leak of fluid and proteins into tissues, extensive leak leads to shock and death. Barriers are largely formed by endothelial cell-cell contacts built up by VE-cadherin and are under the control of RhoGTPases. Here we show that a natural plasmin digest product of fibrin, peptide Bß15-42 (also called FX06), significantly reduces vascular leak and mortality in animal models for Dengue shock syndrome. The ability of Bß15-42 to preserve endothelial barriers is confirmed in rats i.v.-injected with LPS. In endothelial cells, Bß15-42 prevents thrombin-induced stress fiber formation, myosin light chain phosphorylation and RhoA activation. The molecular key for the protective effect of Bß15-42 is the src kinase Fyn, which associates with VE-cadherin-containing junctions. Following exposure to Bß15-42 Fyn dissociates from VE-cadherin and associates with p190RhoGAP, a known antagonists of RhoA activation. The role of Fyn in transducing effects of Bß15-42 is confirmed in Fyn -/- mice, where the peptide is unable to reduce LPS-induced lung edema, whereas in wild type littermates the peptide significantly reduces leak. Our results demonstrate a novel function for Bß15-42. Formerly mainly considered as a degradation product occurring after fibrin inactivation, it has now to be considered as a signaling molecule. It stabilizes endothelial barriers and thus could be an attractive adjuvant in the treatment of shock.

Download full text files

Export metadata

Additional Services

Share in Twitter Search Google Scholar
Author:Marion Gröger, Waltraud Pasteiner, George Ignatyev, Ulrich Matt, Sylvia Knapp, Alena Atrasheuskaya, Eugenij Bukin, Peter Friedl, Daniela Zinkl, Renate Hofer-Warbinek, Kai ZacharowskiORCiDGND, Peter Petzelbauer, Sonja Reingruber
Parent Title (English):PLoS One
Document Type:Article
Date of Publication (online):2009/04/29
Date of first Publication:2009/04/29
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2009/12/10
Issue:(4): e5391
Copyright Gröger et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Source:PLoS ONE. 2009; 4(4): e5391 ; doi: 10.1371/journal.pone.0005391
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 3.0