Z Gastroenterol 2009; 47 - P4_03
DOI: 10.1055/s-0029-1191922

The scavenger receptor D6 limits acute liver damage by degradation of inflammatory chemokines after injury

M Berres 1, M Moreno Zaldivar 1, P Schmitz 1, K Pauels 1, SA Lira 2, C Trautwein 1, F Tacke 1, HE Wasmuth 1
  • 1Medizinische Klinik III RWTH Universitätsklinikum Aachen
  • 2Immunobiology Center, Mount Sinai School of Medicine, New York, USA

Aims: Chemokines are inflammatory mediators which are involved in acute liver injury. The scavenger receptor D6 is a promiscuous chemokine receptor lacking classical signalling functions. It negatively regulates inflammation by targeting CC chemokines to degradation after internalization in various tissues. However, its function in acute liver injury has yet not been analyzed.

Methods: Acute liver injury was induced by injection of CCl4 (0.6mg/kg body weight) in constitutive D6-/- mice and wild-type littermates (n=6). Mice were sacrificed after 0, 24, 48 and 72 hours. The degree of liver injury was assessed by liver histology (H&E staining) and measurement of serum transaminases. The intrahepatic infiltration of immune cells was quantified by FACS analysis. Protein levels of inflammatory chemokines (CCL2, CCL3, CCL5) within the livers were determined by ELISA and CXCL9, which does not bind to D6, were used as control.

Results: Genetic deletion of D6 leads to a prolonged elevation of serum transaminases after acute liver injury compared to wild-type littermates (P=0.018 at 48h). Histologically D6-/- mice display augmented liver damage and an increased infiltration of inflammatory cells after 24 and 48 hours. The infiltration of inflammatory cells in D6-/- mice is mainly due to a significantly higher amount of T cells within the livers (P=0.01 at 24h and P=0.02 at 48h, FACS) while there is no difference in the relative numbers of NK and NKT cells. Notably, the shift in immune cell populations is associated with increased intrahepatic protein levels of the T-cell associated chemokines CCL2, CCL3 and CCL5 in D6-/- mice (all P<0.05). In contrast, CXCL9 level are not different between groups.

Conclusions: Genetic deletion of the scavenger receptor D6 leads to augmented and prolonged liver damage after liver injury in vivo. These results describe a new type of immune regulation during toxic liver damage and imply a novel pathway for therapeutic strategies.

D6 - acute liver injury - chemokines - scavenger receptor