Lau C L, Daggett W C, Yeatman M F, Chai P, Lin S S, Lodge A J, Chen E P, Diamond L E, Byrne G W, Logan J S, Parker W, Platt J L, Davis R D
Department of Surgery, Duke University Medical Center, Durham, NC, USA.
J Thorac Cardiovasc Surg. 2000 Jul;120(1):29-38. doi: 10.1067/mtc.2000.106841.
Pulmonary transplantation has become the preferred treatment for end-stage lung disease, but application of the procedure is limited because of a paucity of donors. One way to solve donor limitations is to use animal organs as a donor source or xenotransplantation. The current barrier to pulmonary xenotransplantation is the rapid failure of the pulmonary xenograft. Although antibodies are known to play a role in heart and kidney xenograft rejection, their involvement in lung dysfunction is less defined. This project was designed to define the role of antibodies in pulmonary graft rejection in a pig-to-baboon model.
Orthotopic transgenic swine left lung transplants were performed in baboons depleted of antibodies by one of three techniques before transplantation: (1) ex vivo swine kidney perfusion, (2) total immunoglobulin-depleting column perfusion, and (3) ex vivo swine lung perfusion. Results were compared with those of transgenic swine lung transplants in unmodified baboons.
All three techniques of antibody removal resulted in depletion of xenoreactive antibodies. Only pretransplantation lung perfusion improved pulmonary xenograft function compared with lung transplantation in unmodified baboons.
The pathogenesis of pulmonary injury in a swine-to-primate transplant model is different from that in renal and cardiac xenografts. Depletion of antibodies alone does not have a beneficial effect and may actually be detrimental.
肺移植已成为终末期肺病的首选治疗方法，但由于供体短缺，该手术的应用受到限制。解决供体限制的一种方法是使用动物器官作为供体来源或进行异种移植。目前肺异种移植的障碍是肺异种移植物迅速衰竭。虽然已知抗体在心脏和肾脏异种移植排斥反应中起作用，但它们在肺功能障碍中的作用尚不清楚。本项目旨在确定猪到狒狒模型中抗体在肺移植排斥反应中的作用。
在移植前通过三种技术之一使狒狒体内抗体耗竭后，将原位转基因猪左肺移植到狒狒体内：（1）离体猪肾灌注，（2）全免疫球蛋白清除柱灌注，（3）离体猪肺灌注。将结果与未处理的狒狒接受转基因猪肺移植的结果进行比较。
所有三种去除抗体的技术均导致异种反应性抗体耗竭。与未处理的狒狒进行肺移植相比，只有移植前肺灌注改善了肺异种移植物的功能。
猪到灵长类动物移植模型中肺损伤的发病机制与肾和心脏异种移植不同。单独去除抗体没有有益作用，实际上可能有害。
