Saumweber D M, Bergmann R, Gokel M, Hammer C
Institute for Surgical Research, Ludwig Maximilians University, Klinikum Grosshadern, Munich, Germany.
Transplantation. 1994 Feb;57(3):358-63.
The pharmacologic modulation of the platelet-activating factor antagonist WEB 2086BS on the release of metabolites of the arachidonic acid and the cytokine TNF alpha was investigated in an ex vivo xenograft model of hyperacute rejection. Pig kidneys were perfused for 60 min in a perfusion system with oxygenated heparinized human or autologous porcine 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-activating factor antagonist WEB 2086BS resulted in a significantly reduced liberation of the cytokine TNF alpha and of prostanoids. The histological findings verified that a hyperacute rejection in the xenogeneic 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 receptors by receptor-antagonists could be an additional therapeutic mode to control hyperacute rejection in xenogeneic transplantation.
在超急性排斥反应的体外异种移植模型中，研究了血小板活化因子拮抗剂WEB 2086BS对花生四烯酸代谢产物和细胞因子肿瘤坏死因子α释放的药理调节作用。分别在灌注系统中用含氧肝素化人血或自体猪血对猪肾进行60分钟灌注。在自体灌注期间，未检测到介质反应的改变，而异种灌注诱导介质的逐渐释放。血小板活化因子拮抗剂WEB 2086BS治疗导致细胞因子肿瘤坏死因子α和前列腺素的释放显著减少。组织学结果证实，异种灌注器官发生了超急性排斥反应，而WEB 2086BS治疗减轻了这种反应。这一观察结果证实，炎症介质在超急性异种排斥反应中起决定性作用。结果表明，通过受体拮抗剂抑制或操纵介质特异性组织受体可能是控制异种移植中超急性排斥反应的另一种治疗方式。
