Tuso P J, Cramer D V, Yasunaga C, Cosenza C A, Wu G D, Makowka L
Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California.
Transplantation. 1993 Jun;55(6):1375-8. doi: 10.1097/00007890-199306000-00031.
We have examined the nature of the binding of human xenoantibodies to pig liver and kidney vascular endothelium. Our results demonstrate that human serum contains IgM and IgG xenoantibodies that bind to pig vascular endothelium, and that the pattern of antibody binding is similar for both livers and kidneys. Immunohistochemical analysis of pig kidneys after perfusion with human blood demonstrated the binding of both IgM and IgG xenoantibodies, complement (C3), and fibrinogen to the vascular and glomerular endothelium. An ELISA assay of the perfusate after perfusion of 500 ml of human blood through a single pig kidney for 60 min demonstrated a significant reduction in the amount of human IgM (67%) and IgG (55%) binding to pig aortic endothelium. Similar perfusion experiments conducted with pig livers were associated with minimal immunohistochemical evidence of the binding of human xenoantibodies to liver vascular endothelium. Immunofluorescence staining for IgM, IgA, C3, and C1q was negative or minimally positive in the liver vascular endothelium. Sinusoidal endothelium were weakly positive for IgG and fibrinogen. The perfusion of the pig liver with human blood was, however, associated with a significant reduction in the subsequent binding of IgM and IgG to pig kidney vascular endothelium. Pig liver perfusion was also responsible for the removal of both IgM and IgG xenoantibodies capable of reacting with pig aortic endothelium, as measured by an ELISA assay of the perfusate. These results suggest that both pig kidney and livers are capable of absorbing the xenoantibodies that may be responsible for mediating a hyperacute rejection of pig xenografts and that the distribution of the target antigens for these antibodies is similar in the two organs.
我们研究了人源异种抗体与猪肝和肾血管内皮细胞结合的性质。我们的结果表明，人血清中含有能与猪血管内皮细胞结合的IgM和IgG异种抗体，且肝脏和肾脏的抗体结合模式相似。用人血灌注猪肾后的免疫组织化学分析表明，IgM和IgG异种抗体、补体（C3）和纤维蛋白原均与血管和肾小球内皮细胞结合。通过向单个猪肾灌注500ml人血60分钟后对灌注液进行ELISA检测发现，与人主动脉内皮细胞结合的人IgM（67%）和IgG（55%）量显著减少。对猪肝进行的类似灌注实验显示，人异种抗体与肝血管内皮细胞结合的免疫组织化学证据极少。肝血管内皮细胞中IgM、IgA、C3和C1q的免疫荧光染色呈阴性或弱阳性。肝血窦内皮细胞对IgG和纤维蛋白原呈弱阳性。然而，用人血灌注猪肝与随后IgM和IgG与猪肾血管内皮细胞的结合显著减少有关。通过对灌注液进行ELISA检测发现，猪肝灌注还导致了能够与猪主动脉内皮细胞反应的IgM和IgG异种抗体的清除。这些结果表明，猪肾和肝脏都能够吸收可能介导猪异种移植物超急性排斥反应的异种抗体，且这两种器官中这些抗体的靶抗原分布相似。
