Modulation of immunologic reactions between cultured porcine hepatocytes and human sera

In the clinical application of a hybrid artificial liver system using porci ne hepatocytes, some immunologic reactions occur between human serum and po rcine hepatocytes. In this study, we investigated the immunologic mechanism s of the cytotoxic reactions, and we tried to inactivate the human serum cy totoxicity by heating the serum or the addition of nafamostat mesilate; (NM ), Immunologic reaction between human serum and porcine hepatocytes by eval uating the immunochemical response against human IgM, IgG, and C3 was inves tigated. The immunochemical analysis of inactivation by heated human serum (56 degrees C, 30 min) and adding NM were performed. The evaluation of seru m cytotoxicity was as follows: when porcine hepatocytes were cultured with heating the human serum or the addition of NM, the survival ratio was obser ved, Immunochemical reactions against human C3 were all positive, but posit ive reaction against human IgM occurred in only one case (5%); those agains t human Ige were all negative. Both heating the serum and adding NM inhibit ed the immunochemical reaction of human C3. The inhibition of human C3 with NM was dependent on that concentration. Both heating of the serum and addi ng NM to the medium decreased damage of porcine hepatocytes. An immunologic reaction between human serum and porcine hepatocytes in a porcine bioartif icial liver clearly occurred, and this reaction was controlled by heating t he serum and adding NM. We believe that NM is useful in the clinical applic ation of our hybrid artificial liver system.