Breakdown of paraendothelial barrier function during Marburg virus infection is associated with early tyrosine phosphorylation of platelet endothelial cell adhesion molecule-1.
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.
Böckeler
Michael
M
Institute of Physiology, Technical University, Dresden, D-01307, Germany.
Ströher
Ute
U
Seebach
Jochen
J
Afanasieva
Tatiana
T
Suttorp
Norbert
N
Feldmann
Heinz
H
Schnittler
Hans-Joachim
HJ
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
D015703:Antigens, CD; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011505:Protein-Tyrosine Kinases