Immunologic considerations in the use of cultured porcine hepatocytes as a hybrid artificial liver. Anti-porcine hepatocyte human serum.

Cultured porcine hepatocytes with reasonable metabolic functions are a promising bioreactor for a hybrid artificial liver in the treatment of liver failure. A cytotoxic human serum (t-serum) against cultured porcine hepatocytes was accidentally discovered during preliminary experiments, however, which prompted the authors to study the mechanism of the cytotoxicity and the frequency of occurrence of the cytotoxic sera. Among 103 individual sera examined, seven (6.8%) sera showed cytotoxicity to cultured porcine hepatocytes. T-serum heated at 56 degrees C for 30 min completely lost its cytotoxic activity, but the inactivated cytotoxicity was restored by the addition of rabbit complement to the inactivated t-serum. IgM-depleted t-serum produced by 2-mercaptoethanol treatment abolished the cytotoxicity to porcine hepatocytes. The cytotoxic reactions were therefore thought to be mediated by IgM capable of complement activation. Although IgM binding to porcine hepatocytes was also seen in nontoxic sera, the IgM did not activate complement. This implies differences in hepatocyte surface antigens recognized by IgM from t- and nontoxic sera. Before clinical application of a hybrid artificial liver using cultured porcine hepatocytes, detection of cytotoxic human IgM against porcine hepatocytes is necessary, and the means of eliminating the cytotoxic IgM from the hybrid artificial liver system, or of inactivating complement in the system, will be desirable in cases positive for cytotoxic IgM.