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Article first published online: 26 JAN 2007
Copyright © 2007 American Association for the Study of Liver Diseases
Volume 45, Issue 2, pages 369–376, February 2007
How to Cite
Nocito, A., Georgiev, P., Dahm, F., Jochum, W., Bader, M., Graf, R. and Clavien, P.-A. (2007), Platelets and platelet-derived serotonin promote tissue repair after normothermic hepatic ischemia in mice. Hepatology, 45: 369–376. doi: 10.1002/hep.21516
This study was presented at the 93rd Annual Meeting of the Swiss Surgical Society, where it was awarded the 2006 Research Prize.
Potential conflict of interest: Nothing to report.
- Issue published online: 26 JAN 2007
- Article first published online: 26 JAN 2007
- Manuscript Accepted: 25 OCT 2006
- Manuscript Received: 17 AUG 2006
- Olga Mayenfisch Foundation, Zurich, Switzerland
- Swiss National Foundation, Bern, Switzerland. Grant Number: 3200B0-109906
- Gebert Ruef Foundation, Basel, Switzerland
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. (HEPATOLOGY 2007;45:369–376.)