HYPERACUTE REJECTION IN AN EX-VIVO MODEL OF RENAL XENOGRAFTING - ROLEOF THE MEDIATOR RESPONSE AND ITS PHARMACOLOGICAL MANIPULATION BY THE SPECIFIC PLATELET-ACTIVATING-FACTOR ANTAGONIST WEB 2086BS

The pharmacologic modulation of the platelet-activating factor antagon ist WEB 2086BS on the release of metabolites of the arachidonic acid a nd the cytokine TNF alpha was investigated in an ex vivo xenograft mod el of hyperacute rejection. Pig kidneys were perfused for 60 min in a perfusion system with oxygenated heparinized human or autologous porci ne blood, respectively. During autologous perfusion, no alterations in the mediator response could be detected, whereas xenogeneic perfusion induced progressive release of mediators. Treatment by the platelet-a ctivating factor antagonist WEB 2086BS resulted in a significantly red uced liberation of the cytokine TNF alpha and of prostanoids. The hist ological findings verified that a hyperacute rejection in the xenogene ic perfused organs had occurred, which was mitigated by the treatment with WEB 2086BS. This observation confirms that inflammatory mediators play a decisive role in hyperacute xenogeneic rejection. The results suggest that suppression or manipulation of mediator-specific tissue r eceptors by receptor-antagonists could be an additional therapeutic mo de to control hyperacute rejection in xenogeneic transplantation.