P-selectin mediates platelet-endothelial cell interactions and reperfusion injury in the mouse liver in vivo

• Published in: Shock (Augusta, Ga.) Ga.), 2002-12, Vol.18 (6), p.529-535
• Main Authors: Khandoga, Andrej, Biberthaler, Peter, Enders, Georg, Teupser, Daniel, Axmann, Stefan, Luchting, Benjamin, Hutter, Joerg, Messmer, Konrad, Krombach, Fritz
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis - drug effects; Blood Platelets - drug effects; Blood Platelets - pathology; Cell Adhesion - drug effects; Endothelium, Vascular - drug effects; Endothelium, Vascular - pathology; Female; Hemodynamics - drug effects; Liver - blood supply; Liver - drug effects; Liver - enzymology; Liver - pathology; Liver Transplantation; Mice; Mice, Inbred C57BL; P-Selectin - pharmacology; Reperfusion Injury - pathology; Reperfusion Injury - physiopathology
• ISSN: 1073-2322
• DOI: 10.1097/00024382-200212000-00008

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.