Discordant Xenograft Rejection in an Antibody-Free Model

Newborn pigs prevented from suckling colostrum were shown to have less than 0.05 micrograms/ml total immunoglobulin present in their serum. Rabbit heart xenografts transplanted heterotopically into the neck of such pigs were hyperacutely rejected, with a mean survival time of 92 +/- 14 min (mean +/- SD). Pigs which had been allowed to suckle and whose serum contained 10-15 mg/ml maternal immunoglobulin hyperacutely rejected rabbit heart xenografts in 109 +/- 62 min. Histological studies showed no Ig binding but complement component 3 (C3) binding to rabbit hearts placed in immunoglobulin-negative pigs. Prolongation of rabbit heart xenograft survival was achieved by administering cobra venom factor (1 mg/kg) to the pigs pretransplant. These data show hyperacute xenograft rejection in the absence of antibody and suggest that its cause is activation of complement by the alternative pathway.