Non-complement- and complement-activating antibodies synergize to cause rejection of cardiac allografts
Non-complement- and complement-activating antibodies synergize to cause rejection of cardiac allografts
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DOI：
10.1111/j.1600-6143.2004.00334.x
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发表时间：
2004-03-01
影响因子：
8.8
通讯作者：
Wasowska, BA
中科院分区：
文献类型：
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作者：
Rahimi, S;Qian, ZP;Wasowska, BA
同种异体抗体（AlloAbs）是器官移植免疫反应的临床重要组成部分。在实验模型中，B10。A （H-2(A)）心脏移植在C57BL/6 （H2 b）免疫球蛋白敲除（IgKO）受体中的存活时间明显长于野生型（WT）受体。向IgKO受者被动转移50-200马克剂量补体活化IgG2b同种异体抗体，可重建同种异体心脏移植的急性排斥反应。虽然被动转移阈以下剂量的25l g IgG2b或单个100-200马克剂量的非补体激活IgG1同种异体抗体不能恢复IgKO受体的急性排斥反应，但这些同种异体抗体的组合确实引起急性移植排斥反应。组织学上，排斥反应伴随着内皮细胞中血管性血友病因子的增加释放。IgG1 AlloAbs本身不能激活补体，也不能增强IgG2b AlloAbs对补体的激活。然而，IgG1 AlloAbs刺激培养的小鼠内皮细胞产生单核细胞趋化蛋白1 （MCP-1）和中性粒细胞趋化生长相关癌基因α (KC)。tnf - α增强IgG1诱导MCP-1和KC的分泌，这些发现表明非补体激活的同种异体抗体可以通过补体激活的同种异体抗体增强同种异体移植物的损伤。非补体激活的同种异体抗体刺激内皮细胞产生趋化因子，这种作用在促炎细胞因子的环境中增强。
Alloantibodies (AlloAbs) are a clinically significant component of the immune response to organ transplants. In our experimental model, B10. A (H-2(a)) cardiac transplants survived significantly longer in C57BL/6 (H2 b) immunoglobulin knock-out (IgKO) recipients than in their wild-type (WT) counterparts. Passive transfer of a single 50-200-mug dose of complement-activating IgG2b AlloAbs to IgKO recipients reconstituted acute rejection of cardiac allografts. Although passive transfer of a subthreshold dose of 25 l g of IgG2b or a single 100-200-mug dose of non-complement-activating IgG1 AlloAbs did not restore acute rejection to IgKO recipients, a combination of these AlloAbs did cause acute graft rejection. Histologically, rejection was accompanied by augmented release of von Willebrand factor from endothelial cells. IgG1 AlloAbs did not activate complement on their own and did not augment complement activation by IgG2b AlloAbs. However, IgG1 AlloAbs stimulated cultured mouse endothelial cells to produce monocyte chemotactic protein 1 (MCP-1) and neutrophil chemoattractant growth-related oncogene alpha (KC). TNF-alpha augmented IgG1 induced secretion of MCP-1 and KC. These findings indicate that non-complement-activating AlloAbs can augment injury to allografts by complement-activating AlloAbs. Non-complement-activating AlloAbs stimulate endothelial cells to produce chemokines and this effect is augmented in the milieu of proinflammatory cytokines.