THE MECHANISM OF DISCORDANT XENOGRAFT REJECTION

TLDR

The study investigated the mechanism of discordant xenograft rejection in a guinea pig‑to‑rat heart graft model. In vitro, rat complement attacked guinea pig erythrocytes through the alternative pathway. Rejection occurred rapidly (≈17.5 min), was prolonged by cobra venom factor pretreatment, and was driven by primary alternative‑pathway complement activation (C3 reduction, intact C4/C2, low natural antibody and CDC/HA titers) with histology showing myocytolysis without infiltration.

Abstract

The mechanism of discordant xenograft rejection using the guinea pig-to-rat heart graft model was studied. In this model, we found that (A) Rejection occurred rapidly, in 17.5 +/- 8.3 min (mean +/- SD) (n = 8). (B) The graft survived longer when the recipient rat was pretreated with cobra venom facter (CVF). (C) Complement hemolytic titers in serum showed significant reduction of C3 in rejection without consumption of C4 and C2, suggesting complement activation through the alternative pathway. (D) No natural antibodies were detected in this combination. Complement-dependent cytotoxicity (CDC) titer, and hemagglutination (HA) titer were lower than x1. (E) Histological examination of the rejected heart xenograft revealed a large area of myocytolysis without interstitial cellular infiltration. (F) In vitro experiments showed that rat complement attacked guinea pig erythrocytes (Egp) via the alternative pathway. These findings indicate that rejection in this discordant xenograft model of guinea pig-to-rat was caused by primary activation of complement via the alternative pathway.