EARLY RECIPIENT-DONOR SWITCH OF THE COMPLEMENT TYPE AFTER LIVER XENOTRANSPLANTATION

Liver transplantation is an immunological peculiarity with respect to the resistance of the graft to humoral rejection. We undertook a kinet ic analysis of molecules involved in humoral rejection for a period of one week following xenografting in the hamster to rat model system. A complement-dependent lymphocytotoxicity test (CDC) was used to detect anti-donor antibodies in the recipient rats. Complement was studied b y two methods. Function of the classical complement pathway was evalua ted with a hemolytic assay, and C3 was measured by radial immunodiffus ion. Conversion of the major plasma proteins from recipient to donor p rofile was studied by zone electrophoresis on agarose. CDC showed anti body titers rose during the first week posttransplantation, and they w ere of complement-activating isotypes. Zone electrophoresis showed alm ost complete replacement of rat C3 by hamster C3 within 72 hours. Hemo lytic assay of complement on day 6 post-transplant showed serum of the xenograft recipients could lyse erythrocytes sensitized with rat anti body with 80% of efficiency of normal rat serum. Our data show the eff ector molecules for humoral rejection, rat antibodies with anti-hamste r specificity and a functional complement cascade, were present within the first week following transplantation. Rapid conversion of serum c omplement to hamster proteins maintains compatibility with the species -specific membrane inhibitors of complement activation expressed by th e xenografted hepatocytes, and could limit complement-mediated damage.