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Aggravation of viral hepatitis by platelet-derived serotonin

Item Type:Article
Title:Aggravation of viral hepatitis by platelet-derived serotonin
Creators Name:Lang, P.A. and Contaldo, C. and Georgiev, P. and El-Badry, A.M. and Recher, M. and Kurrer, M. and Cervantes-Barragan, L. and Ludewig, B. and Calzascia, T. and Bolinger, B. and Merkler, D. and Odermatt, B. and Bader, M. and Graf, R. and Clavien, P.A. and Hegazy, A.N. and Loehning, M. and Harris, N.L. and Ohashi, P.S. and Hengartner, H. and Zinkernagel, R.M. and Lang, K.S.
Abstract:More than 500 million people worldwide are persistently infected with hepatitis B virus or hepatitis C virus. Although both viruses are poorly cytopathic, persistence of either virus carries a risk of chronic liver inflammation, potentially resulting in liver steatosis, liver cirrhosis, end-stage liver failure or hepatocellular carcinoma. Virus-specific T cells are a major determinant of the outcome of hepatitis, as they contribute to the early control of chronic hepatitis viruses, but they also mediate immunopathology during persistent virus infection. We have analyzed the role of platelet-derived vasoactive serotonin during virus-induced CD8(+) T cell-dependent immunopathological hepatitis in mice infected with the noncytopathic lymphocytic choriomeningitis virus. After virus infection, platelets were recruited to the liver, and their activation correlated with severely reduced sinusoidal microcirculation, delayed virus elimination and increased immunopathological liver cell damage. Lack of platelet-derived serotonin in serotonin-deficient mice normalized hepatic microcirculatory dysfunction, accelerated virus clearance in the liver and reduced CD8(+) T cell-dependent liver cell damage. In keeping with these observations, serotonin treatment of infected mice delayed entry of activated CD8(+) T cells into the liver, delayed virus control and aggravated immunopathological hepatitis. Thus, vasoactive serotonin supports virus persistence in the liver and aggravates virus-induced immunopathology.
Keywords:Blood Platelets, CD8-Positive T-Lymphocytes, Half-Life, Viral Animal Hepatitis, Liver, Lymphocytic Choriomeningitis, Microcirculation, Platelet Count, Serotonin, Animals, Mice
Source:Nature Medicine
Publisher:Nature Publishing Group
Page Range:756-761
Date:July 2008
Official Publication:https://doi.org/10.1038/nm1780
PubMed:View item in PubMed

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