title: P-selectin mediates platelet-endothelial cell interactions and reperfusion injury in the mouse liver in vivo.
abstract: Platelets are suggested to participate in the pathogenesis of hepatic ischemia-reperfusion (I/R) injury. This study was designed to analyze platelet-endothelial cell interactions in the postischemic mouse liver in vivo and to define the role of endothelial versus platelet P-selectin for these interactions. Platelet-endothelial cell interactions were quantitatively analyzed using intravital fluorescence microscopy after lobar hepatic I/R in C57BL/6 wild-type and P-selectin-deficient mice after infusion of ex vivo rhodamine-6G-labeled wild-type and P-selectin-deficient platelets. Reperfusion injury and apoptosis were assessed by established methods. In wild-type animals, hepatic I/R caused significantly enhanced platelet-endothelial cell interactions in terminal arterioles and postsinusoidal venules as well as platelet stagnation in sinusoids. Concomitantly, transaminase and caspase-3 activities were elevated and sinusoidal perfusion was impaired. In contrast, platelet-endothelial cell interactions were nearly absent in arterioles and venules of mice lacking endothelial P-selectin, irrespective of the presence of P-selectin on infused platelets, but still significantly elevated in sinusoids. Simultaneously, sinusoidal perfusion failure was ameliorated, and transaminase- and caspase-3 activities were significantly reduced in P-selectin-deficient mice as compared with wild-type animals. The present intravital microscopic study provides, for the first time, quantitative analyses of platelet-endothelial cell interactions in the postischemic hepatic microcirculation. Our in vivo data show that endothelial P-selectin is critical for postischemic platelet-endothelial cell interactions within hepatic presinusoidal arterioles and postsinusoidal venules. P-selectin deficiency prevents microvascular injury and apoptosis after warm hepatic I/R.
authors.affiliation: Institute for Surgical Research, University of Munich, Germany.
authors.forename: Andrej
authors.initials: A
authors.lastname: Khandoga
authors.forename: Peter
authors.initials: P
authors.lastname: Biberthaler
authors.forename: Georg
authors.initials: G
authors.lastname: Enders
authors.forename: Daniel
authors.initials: D
authors.lastname: Teupser
authors.forename: Stefan
authors.initials: S
authors.lastname: Axmann
authors.forename: Benjamin
authors.initials: B
authors.lastname: Luchting
authors.forename: Joerg
authors.initials: J
authors.lastname: Hutter
authors.forename: Konrad
authors.initials: K
authors.lastname: Messmer
authors.forename: Fritz
authors.initials: F
authors.lastname: Krombach
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects* / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D008099:Liver / Q000098:blood supply / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology*; D016031:Liver Transplantation; D051379:Mice; D008810:Mice, Inbred C57BL; D019007:P-Selectin / Q000494:pharmacology*; D015427:Reperfusion Injury / Q000473:pathology* / Q000503:physiopathology
chemical_list: D019007:P-Selectin