Immunogenic role of Kupffer cells in a rat model of acute liver allograft rejection.

Kupffer cells (KCs) are of bone-marrow origin. After liver transplantation, recipient KCs are supposed to replace donor KCs. On the other hand, KCs are currently hypothesized to play a major immunogenic role in acute liver allograft rejection. In the present study, we investigated the immunogenic role of KCs in acute rat liver allograft rejection. For this purpose, we depleted the donor KCs using intravenous injection of liposome-encapsulated dichloromethylene diphosphonate (DMDP) in the fully allogenic ACI-to-LEW rat liver transplantation model. Kupffer cell depletion was confirmed using monoclonal antibodies ED2. In a first set of experiments, graft survival was evaluated, as were body weight and serum bilirubin changes, after the transplantation. Graft survival time showed no difference between the groups (treated, 12.5 +/- 0.92 days; control, 11.9 +/- 0.80 days). Body weight and serum bilirubin changes were similarly affected in both groups. In a second set of experiments, recipients were killed on day 6 after the transplantation, and rejection was histologically graded from 0 to 4. All grafted livers were judged as grade 3 regardless of treatment. ED2 staining showed KCs repopulation in both untreated and the dichloromethylene diphosphonate treated livers. The results of the present study provide evidence that KCs do not play an important immunogenic role in acute liver allograft rejection of the rat.