van Overdam K A, Verbakel C A, Kouwenhoven E A, van Rooijen N, de Bruin R W, IJzermans J N, Marquet R L
Department of Surgery, Erasmus University Rotterdam, The Netherlands.
Transpl Int. 2000;13 Suppl 1:S504-7. doi: 10.1007/s001470050391.
Hyperacute rejection (HAR) of a discordant xenograft can be avoided by complement manipulation, but delayed xenograft rejection (DXR) still leads to graft loss. It is generally assumed that macrophages and NK cells play key roles in DXR. In the present study the survival times and cellular infiltrate following guinea pig to rat heart transplantation was analyzed in the course of DXR, following aspecific and specific manipulation of macrophages and NK cells. HAR was overcome by a single injection of cobra venom factor 1 day before heart transplantation. To aspecifically reduce the inflammatory response dominating DXR, dexamethasone (DEXA) was given. Treatment with DEXA markedly reduced infiltration by NK cells, macrophages, and granulocytes. It also led to prolonged graft survival times (median survival of 0.4 days, n = 10, P < 0.05). In the second series of experiments the specific roles of NK cells and macrophages in DXR were further assessed. Monoclonal antibody 3.2.3 was used to selectively deplete NK cells. Liposome-encapsulated dichloromethylene biphosphonate was given to achieve macrophage depletion. Neither of these specific treatments, alone or combined, led to prolonged graft survival. Immunohistology revealed that at day 2 after transplantation no NK cells or macrophages were present in grafts from the combined treatment group. Only a mild infiltration of granulocytes was observed. Collectively, these results strongly suggest that NK cells and macrophages are not likely to be pivotal cell types in DXR.
通过补体调控可避免异种移植超急性排斥反应（HAR），但延迟性异种移植排斥反应（DXR）仍会导致移植物丧失。一般认为巨噬细胞和自然杀伤细胞（NK细胞）在DXR中起关键作用。在本研究中，在对巨噬细胞和NK细胞进行非特异性及特异性调控后，分析了豚鼠到大鼠心脏移植在DXR过程中的存活时间和细胞浸润情况。在心脏移植前1天单次注射眼镜蛇毒因子可克服HAR。为非特异性减轻主导DXR的炎症反应，给予地塞米松（DEXA）。DEXA治疗显著减少了NK细胞、巨噬细胞和粒细胞的浸润。它还使移植物存活时间延长（中位存活时间为0.4天，n = 10，P < 0.05）。在第二组实验中，进一步评估了NK细胞和巨噬细胞在DXR中的具体作用。使用单克隆抗体3.2.3选择性清除NK细胞。给予脂质体包裹的二氯亚甲基二膦酸盐以实现巨噬细胞清除。这些特异性治疗单独或联合使用均未导致移植物存活时间延长。免疫组织学显示，移植后第2天，联合治疗组的移植物中不存在NK细胞或巨噬细胞。仅观察到轻度的粒细胞浸润。总体而言，这些结果强烈表明NK细胞和巨噬细胞不太可能是DXR中的关键细胞类型。
