EFFECT OF A PLATELET-ACTIVATING-FACTOR (PAF) RECEPTOR ANTAGONIST ON HYPERACUTE XENOGRAFT REJECTION - EVALUATION IN A PIG KIDNEY-HUMAN BLOODXENOPERFUSION MODEL

In pig to human discordant xenotransplantation, PAF may contribute to the pathogenesis of hyperacute xenograft rejection (HXR). We examined the release of PAF and the effect of a PAF receptor antagonist (BN 520 21) on HXR in a pig kidney-human blood xenoperfusion model. Pig kidney s were perfused with porcine blood (AUTO group, n = 5), human blood (W ETER group, n = 6) or human blood plus BN 52021 (BN group, n = 4), res pectively. In contrast to METER kidneys that never produced urine and were rejected in 15-30 min, the administration of BN 52021 induced a p artial recovery of glomerular filtration rate and allowed kidneys to f unction until the end of the study. The release of PAF and soluble P-s electin, as well as endothelial P-selectin expression and tissue myelo peroxidase (MPO), were much higher in the HETER than in the AUTO group . METER and BN kidneys displayed similar natural xenoantibody titres, CH50, PAF, soluble P-selectin as well as renal immunoglobulin (IgM, Ig G, IgA) and complement (C3. C1q) deposition. However, METER kidneys di splayed a full histologic picture of HXR (mainly interstitial haemorrh age and vascular microthrombi) and BN kidneys had only endothelial cel l swelling, Also, BN 52021 administration attenuated glomerular and va scular P-selectin expression and renal tissue MPO activity. We conclud e that in the pig kidney-human blood xenoperfusion model, PAF is produ ced in higher amounts than in the pig kidney-pig blood autologous comb ination. The administration of BN 52021 exerts a protective effect by means of attenuating the acute inflammatory response and blocking vasc ular microthrombi formation.