The immunosuppressive role of adenosine A2A receptors in ischemia reperfusion injury and islet transplantation.
The immunosuppressive role of adenosine A2A receptors in ischemia reperfusion injury and islet transplantation.
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DOI：
10.2174/157339912803529878
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发表时间：
2012-11
影响因子：
3.3
通讯作者：
Brayman KL
中科院分区：
文献类型：
--
作者：
Chhabra P;Linden J;Lobo P;Okusa MD;Brayman KL
腺苷A2A受体（A2AR）的激活一般通过抑制促炎细胞的激活、降低内皮粘附分子的表达和减少促炎细胞因子介质的释放来减轻炎症。使用选择性A2AR激动剂、拮抗剂、A2AR敲除以及嵌合小鼠进行的大量临床前研究表明，A2AR激动剂在治疗缺血再灌注损伤（IRI）和自身免疫性疾病方面具有治疗潜力。本文综述了A2AR激动剂在小鼠肝、肾、心、肺和中枢神经系统IRI模型中的免疫抑制作用，并详细介绍了A2AR激活对中性粒细胞、巨噬细胞、树突状细胞、自然杀伤细胞、NKT细胞、T效应细胞和CD4+CD25+FoxP3+ T调节细胞的细胞效应。这是在涉及炎症级联反应的细胞因子介质的背景下讨论的。虽然腺苷受体激动剂在各种自身免疫性疾病模型中的作用已被充分证明，但关于A2AR激活在1型糖尿病（T1DM）中的作用的信息很少。对T1DM的发病机制和移植围期早期胰岛排斥反应的概述，提供了关于使用A2AR激动剂作为临床胰岛移植的有益干预措施，促进胰岛移植存活，最大限度地减少早期胰岛损失，减少成功移植所需的胰岛数量，从而增加该手术对更多受体的可用性。总之，在胰岛移植中，A2AR激动剂作为IRI的临床干预和临床免疫抑制方案的辅助手段是值得关注的。
Activation of adenosine A2A receptors (A2AR) reduces inflammation by generally inhibiting the activation of pro-inflammatory cells, decreasing endothelial adhesion molecule expression and reducing the release of proinflammatory cytokine mediators. Numerous preclinical studies using selective A2AR agonists, antagonists, A2AR knockout as well as chimeric mice have suggested the therapeutic potential of A2AR agonists for the treatment of ischemia reperfusion injury (IRI) and autoimmune diseases. This review summarizes the immunosuppressive actions of A2AR agonists in murine IRI models of liver, kidney, heart, lung and CNS, and gives details on the cellular effects of A2AR activation in neutrophils, macrophages, dendritic cells, natural killer cells, NKT cells, T effector cells and CD4+CD25+FoxP3+ T regulatory cells. This is discussed in the context of cytokine mediators involved in inflammatory cascades. Whilst the role of adenosine receptor agonists in various models of autoimmune disease has been well-documented, very little information is available regarding the role of A2AR activation in type 1 diabetes mellitus (T1DM). An overview of the pathogenesis of T1DM as well as early islet graft rejection in the immediate peri-transplantation period offers insight regarding the use of A2AR agonists as a beneficial intervention in clinical islet transplantation, promoting islet graft survival, minimizing early islet loss and reducing the number of islets required for successful transplantation, thereby increasing the availability of this procedure to a greater number of recipients. In summary, the use of A2AR agonists as a clinical intervention in IRI and as an adjunct to clinical immunesuppressive regimen in islet transplantation is highlighted.