Article (Scientific journals)
The chemokine receptor CXCR3 limits injury after acute toxic liver damage
Moreno Zaldivar, Mirko; Berres, Marie-Luise; Sahin, Hacer et al.
2012In Laboratory Investigation, 92 (5), p. 724-734
Peer reviewed


Full Text
The chemokine receptor CXCR3.pdf
Publisher postprint (605.43 kB)

All documents in ORBilu are protected by a user license.

Send to


Keywords :
Chemokine receptor; CXCR3; HMGB1; Immune cells; Liver failure; Neutrophils
Abstract :
[en] Although acute liver failure is a rare disease, its presence is associated with high morbidity and mortality in affected patients. While a contribution of the immune system to the outcome of toxic liver failure is anticipated, functionally relevant immune cell receptors for liver cell damage need to be better defined. We here investigate the relevance of the chemokine receptor CXCR3, which is important for hepatic immune cell infiltration, in a model of experimental acute liver failure. Liver injury was induced by a single intraperitoneal injection of carbon tetrachloride (CCl 4) in CXCR3 -/-, CCR1 -/-, CCR5 -/- and wild-type mice. In this model, CXCR3 -/- mice displayed augmented liver damage compared with all other mouse strains as assessed by liver histology and serum transaminases 24 and 72 h after injury. Phenotypically, CXCR3 -/- mice had significantly reduced intrahepatic NK and NKT cells after injury at all investigated time points (all P≤0.05), but strongly elevated expression levels of IL1-Β, TNF-α and IFN-γ. In line with a functional role of innate immune cells, wild-type mice depleted for NK cells with an anti-ASIALO GM1 antibody before liver injury also displayed increased liver injury after CCl 4 challenge. CXCR3 -/- and NK cell-depleted mice show reduced apoptotic liver cells (TUNEL assay), but more necrotic hepatocytes. Functionally, the augmented liver cell necrosis in CXCR3 -/- and NK cell-depleted mice was associated with increased expression of high mobility group 1 (HMGB1) protein and a consecutive enhanced infiltration of neutrophils into the liver. In conclusion, the results demonstrate a primarily unexpected beneficial role of CXCR3 in acute toxic liver injury. These findings should be taken into account when planning trials with CXCR3 antagonists. © 2012 USCAP, Inc All rights reserved.
Disciplines :
Immunology & infectious disease
Author, co-author :
Moreno Zaldivar, Mirko ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Berres, Marie-Luise
Sahin, Hacer
Nellen, Andreas
Heinrichs, Daniel
Schmitz, Petra
Gassler, Nicolaus
Streetz, Konrad
Trautwein, Christian
Wasmuth, Hermann
External co-authors :
Language :
Title :
The chemokine receptor CXCR3 limits injury after acute toxic liver damage
Publication date :
May 2012
Journal title :
Laboratory Investigation
Volume :
Issue :
Pages :
Peer reviewed :
Peer reviewed
Available on ORBilu :
since 16 May 2016


Number of views
50 (0 by Unilu)
Number of downloads
122 (0 by Unilu)

Scopus citations®
Scopus citations®
without self-citations
WoS citations


Similar publications

Contact ORBilu