Suppression of Acute and Chronic Cardiac Allograft Rejection in Mice by Inhibition of Chemokine Receptor 5 in Combination with Cyclosporine A
Suppression of Acute and Chronic Cardiac Allograft Rejection in Mice by Inhibition of Chemokine Receptor 5 in Combination with Cyclosporine A
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DOI：
10.1016/j.jss.2009.01.014
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发表时间：
2009-11-01
影响因子：
2.2
通讯作者：
Xu, Lei
中科院分区：
文献类型：
--
作者：
Li, Jun;Xia, Jiahong;Xu, Lei
背景。趋化因子受体5 （CCR5）是一种表达于活化T细胞上的趋化因子受体，抑制CCR5是HIV感染患者有效的抗病毒治疗方法，但其在调节炎症和免疫方面的功效才刚刚开始被研究。在这项研究中，我们研究了CCR5与环孢素A联合治疗在心脏移植急性和慢性排斥反应中的抑制作用。材料与方法。80只完全mhc错配的小鼠心脏移植模型随机分为四组。A组小鼠分别给予抗ccr5单抗和CsA治疗，B组小鼠单独给予抗ccr5单抗治疗，C组小鼠仅给予CsA治疗，D组为PBS对照组。分别于移植后第7天和第45天观察急性和慢性排斥反应。与pbs处理组（11.067 +/- 0.707 d）相比，抗ccr5单抗加CsA处理的同种异体移植物存活时间明显延长（44.73 +/- 0.258 d, P < 0.01）。抗ccr5单抗联合CsA治疗可显著抑制cav的进展。我们的研究结果表明，抗ccr5单抗联合CsA可以延长同种异体移植的存活时间，减轻急性和慢性同种异体移植的排斥反应。因此，抗ccr5单抗和CsA联合用药可能成为预防传统免疫抑制剂无法避免的心脏移植衰竭的一种新的治疗方法。(C) 2009爱思唯尔公司版权所有。
Background. Inhibition of chemokine receptor 5 (CCR5), a chemokine receptor expressed on activated T cells, is an effective antiviral therapy in patients with HIV infection, but its efficacy in modulating inflammation and immunity is only just beginning to be investigated. In this study we examined the inhibition of CCR5 in combination with the treatment with cyclosporine A in acute and chronic rejection in cardiac transplantation.Materials and Methods. Eighty fully MHC-mismatched murine cardiac allograft models were randomized to four groups. Recipients in group A were treated with anti-CCR5 mAb and CsA, mice in group B were given anti-CCR5 mAb alone, animals in group C were administered only CsA, and group D were the control group with PBS. Acute and chronic rejection was investigated on day 7 and day 45 post-transplant, respectively.Results. Allografts treated with anti-CCR5 mAb plus CsA showed significantly prolonged survival (44.73 +/- 0.258 d, P < 0.01) compared with PBS-treated group (11.067 +/- 0.707 d). Treatment with anti-CCR5 mAb plus CsA significantly inhibited the progression of CAV.Conclusions. Our findings demonstrated that anti-CCR5 mAb in combination with CsA can prolong the survival of allograft and alleviate both acute and chronic allograft rejection. Thus, combined administration of anti-CCR5 mAb and CsA may become a new therapeutic approach for the prevention of cardiac graft failure that has not been obviated by conventional immunosuppressive agents. (C) 2009 Elsevier Inc. All rights reserved.