title: Breakdown of paraendothelial barrier function during Marburg virus infection is associated with early tyrosine phosphorylation of platelet endothelial cell adhesion molecule-1.
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)- alpha /H2O2 and interferon (IFN)- gamma , 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- alpha /H2O2 that was not due to an opening of the interendothelial junctions. These data indicate 2 distinct mechanisms for the TNF- alpha /H2O2-mediated decrease in endothelial barrier function involving tyrosine phosphorylation of PECAM-1 but not requiring tyrosine phosphorylation of VE-cadherin or catenin proteins.
authors.affiliation: Institute of Physiology, Technical University, Dresden, D-01307, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Böckeler
authors.forename: Ute
authors.initials: U
authors.lastname: Ströher
authors.forename: Jochen
authors.initials: J
authors.lastname: Seebach
authors.forename: Tatiana
authors.initials: T
authors.lastname: Afanasieva
authors.forename: Norbert
authors.initials: N
authors.lastname: Suttorp
authors.forename: Heinz
authors.initials: H
authors.lastname: Feldmann
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Schnittler
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000097:blood; D001792:Blood Platelets / Q000502:physiology*; D004730:Endothelium, Vascular / Q000503:physiopathology* / Q000821:virology; D006801:Humans; D008264:Macrophages / Q000502:physiology / Q000821:virology; D008379:Marburg Virus Disease / Q000097:blood / Q000503:physiopathology*; D029024:Marburgvirus / Q000472:pathogenicity*; D009000:Monocytes / Q000502:physiology / Q000821:virology; D010766:Phosphorylation; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000097:blood* / Q000276:immunology; D011505:Protein-Tyrosine Kinases / Q000097:blood
chemical_list: D015703:Antigens, CD; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011505:Protein-Tyrosine Kinases