Pratt J R, Hibbs M J, Laver A J, Smith R A, Sacks S H
Department of Renal Medicine, Guy's Hospital, London, UK.
Transpl Immunol. 1996 Mar;4(1):72-5. doi: 10.1016/s0966-3274(96)80041-4.
The deposition of complement (C) components on tissues of transplanted organs may induce many proinflammatory responses. The role of such C activation in allograft rejection is uncertain. We addressed this question by inhibiting C at the level of the C3 and C5 convertases, preventing C activation and progression of its cascade, using recombinant human soluble complement receptor 1 (sCR1) in an unsensitized rat renal allograft model. Fully MHC disparate Lewis to DA rat renal allograft recipients given 25 mg/kg sCR1 daily, with saline-treated allograft recipients as controls (n = 15 in each group), were sacrificed from day 1 to day 5 post-transplant, and examined histopathologically, and for the deposition of C3 and C5b-9 membrane attack complex (MAC), and for the presence of leucocyte antigen markers. Treated animals demonstrated a reduction in vascular injury and cellular infiltration, coincident with reduced C deposition. Flow cytometric analysis of leucocyte subpopulations in the spleen showed a reduction in activated (CD25 positive) B and T cells in treated animals, compared to saline treated controls. The results suggest that C inhibition with sCR1, in an unsensitized model of allograft rejection, was able to suppress the vascular and cell mediated components of tissue injury. The data support not only a role for C in antibody and possibly cell mediated cytotoxicity in the graft, but also suggest a role in the primary immune response leading to both T cell and B cell activation.
补体（C）成分在移植器官组织上的沉积可能引发多种促炎反应。这种补体激活在同种异体移植排斥反应中的作用尚不确定。我们通过在C3和C5转化酶水平抑制补体，使用重组人可溶性补体受体1（sCR1），在未致敏的大鼠肾移植模型中阻止补体激活及其级联反应，来解决这个问题。将完全主要组织相容性复合体（MHC）不相容的从Lewis大鼠到DA大鼠的肾移植受体，每天给予25mg/kg sCR1，以生理盐水处理的移植受体作为对照（每组n = 15），在移植后第1天至第5天处死，进行组织病理学检查，检测C3和C5b-9膜攻击复合物（MAC）的沉积以及白细胞抗原标志物的存在情况。接受治疗的动物血管损伤和细胞浸润减少，同时补体沉积也减少。对脾脏中白细胞亚群的流式细胞术分析显示，与生理盐水处理的对照组相比，接受治疗的动物中活化的（CD25阳性）B细胞和T细胞减少。结果表明，在未致敏的同种异体移植排斥模型中，用sCRl抑制补体能够抑制组织损伤的血管和细胞介导成分。这些数据不仅支持补体在移植物中的抗体介导以及可能的细胞介导细胞毒性中的作用，还表明其在导致T细胞和B细胞活化的初次免疫反应中的作用。
