Anti-HLA class I antibodies activate endothelial cells and promote chronic rejection
Anti-HLA class I antibodies activate endothelial cells and promote chronic rejection
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DOI：
10.1097/01.tp.0000153293.39132.44
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发表时间：
2005-02-15
期刊：
影响因子：
6.2
通讯作者：
Reed, EF
中科院分区：
文献类型：
--
作者：
Jin, YP;Jindra, PT;Reed, EF
对同种异体移植物表现出体液免疫反应的移植受者表现出较低的移植物存活率以及发生慢性排斥和移植物动脉硬化的风险增加。我们的研究表明，抗 HLA I 类抗体 (Ab) 通过与 EC 表面的 I 类分子结合并转导细胞内信号，在控制内皮细胞 (EC) 功能中发挥重要作用。抗 HLA Ab 表现出两种主要效应功能：刺激细胞增殖和上调细胞存活基因。重要的是，I 类连接引发的细胞内事件似乎受到抗体浓度的影响。高滴度抗 HLA Ab 刺激细胞增殖，而低滴度 Ab 激活 PI3K/Akt 通路并促进细胞存活蛋白（包括 Bcl-2 和 Bcl-xL）的表达。抗 HLA I 类抗体可能通过促进 EC 存活和增殖而促进慢性同种异体移植排斥过程。
Transplant recipients exhibiting a humoral immune response to the allograft demonstrate lower graft survival and increased risk for the development of chronic rejection and transplant arteriosclerosis. Our studies suggest that anti-HLA class I antibodies (Ab) play an important role in controlling endothelial cell (EC) function by binding to class I molecules on the surface of the EC and transducing intracellular signals. Anti-HLA Ab exhibit two primary effector functions: stimulation of cell proliferation and up-regulation of cell survival genes. Importantly, the intracellular events initiated by class I ligation appear to be influenced by the concentration of the Ab. High-titered anti-HLA Ab stimulate cell proliferation whereas low-titered Ab activate the PI3K/Akt pathway and promote expression of cell survival proteins including Bcl-2 and Bcl-xL. Anti-HLA class I Ab may contribute to the process of chronic allograft rejection by promoting EC survival and proliferation.