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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-8198

Lang, P A; Contaldo, C; Georgiev, P; El-Badry, A M; Recher, M; Kurrer, M; Cervantes-Barragan, L; Ludewig, B; Calzascia, T; Bolinger, B; Merkler, D; Odermatt, B; Bader, M; Graf, R; Clavien, P A; Hegazy, A N; Löhning, M; Harris, N L; Ohashi, P S; Hengartner, H; Zinkernagel, R M; Lang, K S (2008). Aggravation of viral hepatitis by platelet-derived serotonin. Nature Medicine, 14(7):756-761.

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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.

Item Type:Journal Article, refereed, further contribution
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Reconstructive Surgery
04 Faculty of Medicine > University Hospital Zurich > Institute of Surgical Pathology
04 Faculty of Medicine > University Hospital Zurich > Clinic for Visceral and Transplantation Surgery
04 Faculty of Medicine > University Hospital Zurich > Institute of Experimental Immunology
04 Faculty of Medicine > University Hospital Zurich > Division of Surgical Research
DDC:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2008
Deposited On:16 Dec 2008 13:27
Last Modified:27 Nov 2013 21:30
Publisher:Nature Publishing Group
ISSN:1078-8956
Publisher DOI:10.1038/nm1780
PubMed ID:18516052
Citations:Web of Science®. Times Cited: 68
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Scopus®. Citation Count: 76

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