EVIDENCE THAT INTRAVENOUSLY ADMINISTERED ALPHA-GALACTOSYL CARBOHYDRATES REDUCE BABOON SERUM CYTOTOXICITY TO PIG-KIDNEY CELLS (PK15) AND TRANSPLANTED PIG HEARTS

Methods of inhibiting the hyperacute antibody-mediated rejection that occurs when pig organs are transplanted into primates have been invest igated using the baboon as a potential recipient. Baboons were treated with different regimens that included combinations of (1) splenectomy , (2) pharmacologic immunosuppression (CsA, cyclophosphamide, corticos teroids +/- methotrexate), and (3) intravenous infusion of oligosaccha rides. The cytotoxicity of the serum was then assessed on cultures of pig kidney cells (PK15). Unmodified serum caused approximate 65-100% p ig cell destruction. Splenectomy and/or pharmacologic immunosuppressio n, and infusions of dextran, dextrose or mannitol, did not result in a ny reduction of cytotoxicity. Infusions of melibiose and/or arabinogal actan, both of which have terminal non-reducing alpha-galactose, howev er, decreased relative PK15 cell damage significantly in a dose-depend ent manner. At high concentrations (less than or equal to 50 g/hr), co mplete inhibition of cytotoxicity was achieved in 4 of 15 baboons. The extracorporeal immunoadsorption of baboon serum utilizing immunoaffin ity columns of melibiose also resulted in a significant reduction (of approximate to 80%) in cytotoxic effect. In 1 baboon, melibiose and ar abinogalactan infusion delayed vascular rejection of a pig cardiac xen ograft from 10 min to about 12 hr, at which time the baboon died from the toxic effects of the carbohydrate infusion. These observations (1) add further support to the role that anti-alpha-galactosyl antibodies play in the hyperacute rejection of pig tissues transplanted into pri mates, and (2) demonstrate that serum cytotoxicity can be reduced by t he intravenous infusion of alpha-galactosyl oligosaccharides or by ext racorporeal immunoadsorption using these carbohydrates.