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Int J Clin Exp Pathol 2013;6(4):678-685

Original Article
Met-CCL5 modifies monocyte subpopulations during liver fibrosis re-gression

Miriam K Stock, Linda Hammerich, Nicole T do O, Marie-Luise Berres, Muhammad Alsamman, Daniel Heinrichs, Andreas Nellen, Christian
Trautwein, Frank Tacke, Hermann E Wasmuth, Hacer Sahin

Department of Medicine III, RWTH University Hospital Aachen, Pauwelsstrasse 30, D-52074 Aachen, Germany

Received January 22, 2013; Accepted February 19, 2013; Epub March 15, 2013; Published April 1, 2013

Abstract: Fibrosis or scarring of the liver parenchyma is a mainstay of chronic liver diseases and is associated with increased morbidity and
mortality. Since complete scarring of the liver develops over several decades, therapeutic intervention with the aim of ameliorating fibrosis is of
great clinical interest. In a recent study, we could identify the chemokine receptor antagonist Met-CCL5 as a potential compound to inhibit
fibrosis progression and accelerate its regression. In the current study we characterized immune changes during fibrosis regression
associated with the treatment with the CCL5 (RANTES) chemokine receptor antagonist Met-CCL5 in an established mouse model of chronic
liver damage. Met-CCL5 or PBS was given after fibrosis induction (8 weeks of CCl4) and mice were sacrificed three and seven days after peak
fibrosis. Mouse livers were analyzed for immune cell infiltration and cytokine gene expression. The results show that overall monocyte
recruitment was not affected by Met-CCL5, but there was a significant shift to a pro-inflammatory Gr1+ monocyte population in the livers of mice
treated with Met-CCL5. These monocytes were mostly iNOS +, a phenomenon which was also evident when analyzing the overall gene
expression profiles in the livers. Since a shift in monocyte subpopulations has recently been identified to contribute to fibrosis regression, our
results help explaining the efficacy of CCL5 chemokine antagonism as a novel treatment option for fibrotic liver diseases. (IJCEP1301049).

Keywords: Met-CCL5, chemokines, liver fibrosis, fibrosis regression

Address correspondence to: Dr. Hacer Sahin, Medical Department III, University Hospital Aachen, RWTH Aachen, Pauwelsstrasse 30,
D-52057 Aachen, Germany. Phone: ++49 241 8080861; Fax: ++49 241 8082455; E-mail: hasahin@ukaachen.de