Schilling A, Land W, Pratschke E, Pielsticker K, Brendel W
Surg Gynecol Obstet. 1976 Jan;142(1):29-32.
Xenotransplantation in distantly related donor-recipient systems is rejected within minutes. According to present theories, hyperacute rejection is due to preformed antibodies. However, our results suggest that a nonimmunologic reaction plays a dominant role in the hyperacute rejection reaction. To analyze the hyperacute rejection reaction, a previously described model of isolated in vitro xenohemoperfusion was used in which rat kidneys were perfused with dog blood at constant pressure. Rejection criterion was cessation of xenograft perfusion flow rate with constant perfusion pressure and histologic findings of aggregation of thrombocytes and endothelial lesions. In our experimental approach, the donor kidney was perfused with separate cellular and humoral components of the recipient blood with redetection of the rejection activity in one of the recipient blood components. Each blood component was tested for preformed antibody before hemoperfusion. In control studies, xenoperfusion of rat kidneys with whole blood from the dog always resulted in hyperacute rejection. In contrast, allogenic perfusion with whole blood caused no rejection. In three groups, typical hyperacute rejection occurred. Perfusion with whole blood from newborn dogs; no preformed antibodies in vitro; perfusion with reactivated dog whole blood containing no preformed xenohemoagglutinating antibodies, which had been eliminated by adsorption, and perfusion with reactivated dog whole blood containing no preformed xenocomplement fixing antibodies also eliminated by adsorption, all resulted in hyperacute rejection. Whole blood from newborn dogs and reactivated, adsorbed antibody-free whole blood from dogs contained active complement. Perfusion of rat kidneys with heat decomplemented, antibody-containing or antibody-free dog blood showed no hyperacute rejection reaction. The addition of fresh complement to these last two groups resulted in typical hyperacute rejection.
远亲供体-受体系统中的异种移植在数分钟内就会被排斥。根据目前的理论，超急性排斥反应是由预先形成的抗体引起的。然而，我们的结果表明，非免疫反应在超急性排斥反应中起主导作用。为了分析超急性排斥反应，我们使用了一种先前描述的体外异种血液灌注模型，在该模型中，大鼠肾脏在恒定压力下用狗的血液进行灌注。排斥标准是在恒定灌注压力下异种移植灌注流速停止，以及血小板聚集和内皮病变的组织学发现。在我们的实验方法中，供体肾脏用受体血液的单独细胞和体液成分进行灌注，并在受体血液成分之一中重新检测排斥活性。在血液灌注前，对每个血液成分进行预先形成抗体的检测。在对照研究中，用狗的全血对大鼠肾脏进行异种灌注总是导致超急性排斥反应。相比之下，用全血进行同种异体灌注不会引起排斥反应。在三组中发生了典型的超急性排斥反应。用新生狗的全血灌注；体外无预先形成的抗体；用不含预先形成的异种血凝抗体（已通过吸附消除）的重新激活的狗全血灌注，以及用同样通过吸附消除了预先形成的异种补体结合抗体的重新激活的狗全血灌注，均导致超急性排斥反应。新生狗的全血和重新激活的、不含吸附抗体的狗全血含有活性补体。用热灭活补体的、含抗体或不含抗体的狗血液灌注大鼠肾脏未显示超急性排斥反应。向最后两组添加新鲜补体导致典型的超急性排斥反应。
