Collins B H, Chari R S, Magee J C, Harland R C, Lindman B J, Logan J S, Bollinger R R, Meyers W C, Platt J L
Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710.
Transplantation. 1994 Dec 15;58(11):1162-71.
Hyperacute rejection of renal and cardiac xenografts is initiated by the reaction of recipient natural antibodies and complement with endothelial cell antigens of the donor organ. The liver is thought to be less susceptible to this form of rejection; however, the mechanisms underlying its decreased susceptibility are not known. We investigated the organ injury occurring in porcine livers perfused with blood from 4 human subjects with fulminant hepatic failure. Nine porcine livers were perfused via an extracorporeal circuit in order to provide temporary metabolic support. Each porcine liver exhibited metabolic function, and the duration of xenoperfusion ranged from 2 to 5 hr. Histologic examination of the xenoperfused livers revealed focal hepatocellular necrosis, prominent infiltration of neutrophils, and, in 7 of 9 cases, periportal and centrilobular hemorrhage and thrombosis. Immunopathology demonstrated minimal or no human IgM and IgG along the small vessels and sinusoidal surfaces. Trace deposits of human IgM were observed along the luminal surfaces of large blood vessels in most cases. Trace deposits of C3 were noted in 2 of 9 livers; however, C4, iC3b, C5b, properdin, and the membrane attack complex were not detected. Human anti-porcine natural antibody titers decreased less than expected during the perfusions. Serum CH50, C3, and C4 levels were low before each procedure and decreased slightly with perfusion. One patient perfused 2 porcine livers and a human liver. The human liver had focal hepatocellular necrosis, trace deposits of IgM, no deposits of complement, and an infiltrate consisting of neutrophils; however, the neutrophil influx was less than that observed in the xenoperfused livers. To further evaluate the effects of alloperfusion, venovenous bypass was established in 2 pigs and the extracorporeal circuit was utilized to perfuse 2 porcine livers. The alloperfused porcine livers had focal hepatocellular necrosis and a minimal infiltrate of neutrophils. There were no deposits of porcine IgM, IgG, or complement components. In conclusion, although the porcine livers perfused by human blood sustained structural damage, the time course, the absence of immune deposits, and the findings of similar, albeit less severe, lesions in the alloperfused livers suggest that the pathogenesis of tissue injury in the xenoperfused livers differs from that of hyperacute rejection and may be related to the action of recipient neutrophils.
肾和心脏异种移植的超急性排斥反应是由受者天然抗体和补体与供体器官的内皮细胞抗原反应引发的。肝脏被认为对这种排斥形式不太敏感；然而，其敏感性降低的潜在机制尚不清楚。我们研究了用4名暴发性肝衰竭人类受试者的血液灌注的猪肝中发生的器官损伤。通过体外循环灌注9个猪肝，以提供临时代谢支持。每个猪肝都表现出代谢功能，异种灌注持续时间为2至5小时。对异种灌注肝脏的组织学检查显示局灶性肝细胞坏死, 中性粒细胞显著浸润，并且在9例中的7例中，门周和小叶中心有出血和血栓形成。免疫病理学显示沿小血管和窦状表面的人IgM和IgG极少或没有。在大多数情况下，在大血管腔表面观察到微量人IgM沉积。在9个肝脏中的2个中发现微量C3沉积；然而，未检测到C4、iC3b、C5b、备解素和膜攻击复合物。在灌注过程中，人抗猪天然抗体滴度下降低于预期。每次手术前血清CH50、C3和C4水平较低，灌注后略有下降。一名患者灌注了2个猪肝和1个人肝。人肝有局灶性肝细胞坏死、微量IgM沉积、无补体沉积，并有中性粒细胞浸润；然而，中性粒细胞流入量少于在异种灌注肝脏中观察到的情况。为了进一步评估同种灌注的影响，在2头猪中建立了静脉-静脉旁路，并利用体外循环灌注2个猪肝。同种灌注的猪肝有局灶性肝细胞坏死和微量中性粒细胞浸润。没有猪IgM、IgG或补体成分的沉积。总之，尽管用人血灌注的猪肝遭受了结构损伤，但时间进程、免疫沉积物的缺乏以及同种灌注肝脏中类似但较轻病变的发现表明，异种灌注肝脏中组织损伤的发病机制与超急性排斥反应不同，可能与受者中性粒细胞的作用有关。
