Hepatocyte transplantation - in vitro cytotoxic reaction of autologous granulocytes and mononuclears to isolated hepatocytes
H L Olszewski, H Hiwot, B Interewicz, A Rudowska, E Szyper, B Meener
Ann Transplant 1999; 4(3-4): 11-16
Hepatocyte (He) transplantation (tx) may be useful for bridging patients to whole organ transplantation and for providing metabolic support during liver failure and for replacing whole organ transplantation in certain liver metabolic diseases. In specific situations where the death rate of host hepatocytes is high, the transplanted cells can repopulate the native liver. Successful transplantation of hepatocytes is hampered by lack of proper cellular (stromal) and humoral (cytokines) environment at the site of implantation. We have found that another factor responsible for low in vivo survival rate of transplanted HC is their rapid destroying by host granulocytes and monocytes. AIM. In this study we investigated the in vitro process of destruction of HC by granulocytes and mononuclear cells, the phenotypes of effector mononuclears and the tempo of HC lysis. Methods: In vitro cell-mediated cytotoxicity, HC-PMN and HC-PBM rosette formation rate and HC lysis, as well as phenotypes of HC-adhering cells were investigated. RESULTS. Granulocytes formed rosettes with HC almost immediately after the beginning of incubation and were found highly cytotoxic to HC. The cellular mechanism of lysis was not mediated by serum natural antibodies. Also the in vitro mixed HC-granulocyte 51Cr test showed high granulocyte cytolytic activity. Monoclonal antibodies to class I and II antigens, CD 11/18 and 54 did not block the granulocyte cytotoxicity. Blood mononuclear cells also formed rosettes with HC and were cytotoxic to them, but the level of cytotoxicity was lower than of granulocytes. ED I + monocytes revealed highest cytolytic activity toward HC. Hepatocyte contained only trace levels of endotoxin and no chemotactic activity of granulocytes and monocytes toward HC could be observed. Conclusions:A random physical contact of blood leukocytes seems necessary for adhesion to isolated HC. Taken together, granulocytes and monocytes recognize intercellular surface molecules on HC "exposed during isolation" from the hepatic trabeculae as "non-self' and lyse HC by direct contact.
Keywords: hepatocyte, Transplantation, Granulocyte, monocyte, cytotoxicity