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Platelets and platelet-derived serotonin promote tissue repair after normothermic hepatic ischemia in mice

Item Type:Article
Title:Platelets and platelet-derived serotonin promote tissue repair after normothermic hepatic ischemia in mice
Creators Name:Nocito, A., Georgiev, P., Dahm, F., Jochum, W., Bader, M., Graf, R. and Clavien, P.A.
Abstract:Hepatic ischemia and reperfusion (I/R) leads to the formation of leukocyte-platelet aggregates. Upon activation, platelets generate reactive oxygen species and release proapoptotic and proinflammatory mediators as well as growth factors. In cold hepatic ischemia, adhesion of platelets to endothelial cells mediates sinusoidal endothelial cell apoptosis. Furthermore, platelet-derived serotonin mediates liver regeneration. We hypothesized that platelets may contribute to reperfusion injury and repair after normothermic hepatic ischemia. The aim of this study was to assess the impact of platelets in normothermic hepatic I/R injury using models of impaired platelet function and immune thrombocytopenia. Inhibition of platelet function in mice was achieved via clopidogrel feeding. Immune thrombocytopenia was induced via intraperitoneal injection of anti-CD41 antibody. Platelet-derived serotonin was investigated using mice lacking tryptophan hydroxylase 1. Mice were subjected to 60 minutes of partial hepatic ischemia and various time points of reperfusion. Hepatic injury was determined via AST and histological analysis of the necrotic area as well as leukocyte infiltration. Liver regeneration was determined via proliferating cell nuclear antigen and Ki67 immunohistochemistry. Neither inhibition of platelet function nor platelet depletion led to a reduction of I/R injury. Liver regeneration and repair were significantly impaired in platelet-depleted animals. Mice lacking peripheral serotonin were deficient in hepatocyte proliferation, but otherwise displayed normal tissue remodeling. CONCLUSION: Platelets have no direct impact on the pathogenesis of normothermic I/R injury. However, they mediate tissue repair and liver regeneration. Furthermore, platelet-derived serotonin is a mediator of hepatocyte proliferation in the postischemic liver, but has no impact on tissue remodeling.
Keywords:Blood Platelets, Cell Movement, Cell Proliferation, Cytokines, Leukocytes, Liver Regeneration, Platelet Count, Reperfusion Injury, Serotonin, Temperature, Thrombocytopenia, Tryptophan Hydroxylase, Animals, Mice
Page Range:369-376
Date:February 2007
Official Publication:https://doi.org/10.1002/hep.21516
PubMed:View item in PubMed

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