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Michael Böckeler, Ute Ströher, Jochen Seebach, Tatiana Afanasieva, Norbert Suttorp, Heinz Feldmann, Hans-Joachim Schnittler, Breakdown of Paraendothelial Barrier Function during Marburg Virus Infection Is Associated with Early Tyrosine Phosphorylation of Platelet Endothelial Cell Adhesion Molecule—1, The Journal of Infectious Diseases, Volume 196, Issue Supplement_2, November 2007, Pages S337–S346, https://doi.org/10.1086/520606
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Abstract
Marburg virus (MARV) infection often causes fulminant shock due to pathologic immune responses and alterations of the vascular system. Cytokines released from virus-infected monocytes/macrophages provoke endothelial activation and vascular hyperpermeability and contribute to the development of shock. Tyrosine phosphorylation of cell-junction proteins is important for the regulation of paraendothelial barrier function. We showed that mediators released from MARV-infected monocytes/macrophages, as well as recombinant tumor necrosis factor (TNF)-α/H2O2 and interferon (IFN)-γ, caused tyrosine phosphorylation of platelet endothelial cell adhesion molecule-1 (PECAM-1) but not of the vascular endothelial (VE) cadherin/catenin complex proteins. Tyrosine phosphorylation of PECAM-1 was associated with delayed opening of interendothelial junctions. Interestingly, we observed an early increase in water permeability in response to TNF-α/ H2O2 that was not due to an opening of the interendothelial junctions. These data indicate 2 distinct mechanisms for the TNF-α/H2O2-mediated decrease in endothelial barrier function involving tyrosine phosphorylation of PECAM-1 but not requiring tyrosine phosphorylation of VE-cadherin or catenin proteins.
- cytokine
- tumor necrosis factors
- endothelial cells
- immune response
- cd31 antigens
- cadherins
- endothelium
- hydrogen peroxide
- intercellular junctions
- interferons
- macrophages
- marburg virus disease
- monocytes
- permeability
- phosphorylation
- shock
- infections
- tyrosine
- marburg virus
- human leukocyte interferon
- catenins