Hepatocyte transplantation - Granulocytes and mononuclear cells recognize the surface of isolated autologous hepatocytes as non-self and destroy them

Abstract

Successful transplantation of hepatocytes (HC) is hampered by lack of a proper cellular (stromal) and humoral (cytokines) environment at the site of implantation. We have found that another factor responsible for the low survival rate of transplanted HC is their rapid destruction by host granulocytes. In this study we have investigated the mechanism of the rapid elimination of transplanted hepatocytes in a syngeneic and allogeneic recipient. Only 10% of the radioactivity of syngeneic (LEW-LEW) or allogeneic (BN-LEW) HC was recovered in recipient lymphoid tissues 6 h after i.v. infusion. Pretreatment of the recipient with Endoxan or sublethal irradiation brought about an increased accumulation of HC radioactivity in lungs and spleen, indicating the entrament of live cells in these organs. Only a few HC could be seen in the liver 6 h after intraportal infusion. Granulocytes were found to be cytotoxic to HC in vitro (39%). Monoclonal antibodies to class I and II antigens, CD 11/18 and 54, did not block the granulocyte cytotoxicity. Granulocyte and HC cluster formation could be seen on smears from a drop of mixed cultures, the rates of formation increasing with the time of incubation. Two out of 34 monoclonal antibodies to HC surface molecules partly blocked the granulocyte cytotoxicity. No evident differences in the elimination rate and in in vitro cytotoxicity were seen between the syngeneic and allogeneic HC. © Springer-Verlag 1998.