Breakdown of Paraendothelial Barrier Function during Marburg Virus Infection Is Associated with Early Tyrosine Phosphorylation of Platelet Endothelial Cell Adhesion Molecule—1

• Published in: The Journal of infectious diseases 2007-11, Vol.196 (Supplement-2), p.S337-S346
• Main Authors: Böckeler, Michael, Ströher, Ute, Seebach, Jochen, Afanasieva, Tatiana, Suttorp, Norbert, Feldmann, Heinz, Schnittler, Hans-Joachim
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; Antigens, CD - blood; Biological and medical sciences; Blood Platelets - physiology; Catenins; Cell adhesion; Cytokines; Ebola virus; Endothelial cells; Endothelium, Vascular - physiopathology; Endothelium, Vascular - virology; Fundamental and applied biological sciences. Psychology; Humans; Infections; Macrophages - physiology; Macrophages - virology; Marburg Virus Disease - blood; Marburg Virus Disease - physiopathology; Marburgvirus - pathogenicity; Microbiology; Miscellaneous; Monocytes - physiology; Monocytes - virology; Phosphorylation; Physiological regulation; Platelet Endothelial Cell Adhesion Molecule-1 - blood; Platelet Endothelial Cell Adhesion Molecule-1 - immunology; Protein-Tyrosine Kinases - blood; Proteins; Viral Pathogenesis; Virology
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/520606

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.