Prolonged rosmarinic survival of islet allografts in mice treated with acid and anti-CD154 antibody
Prolonged rosmarinic survival of islet allografts in mice treated with acid and anti-CD154 antibody
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DOI：
10.3858/emm.2008.40.1.1
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发表时间：
2008-02-29
影响因子：
12.8
通讯作者：
Kim, Sung-Joo
中科院分区：
文献类型：
--
作者：
Jung, Da-Yeon;Kim, Eun-Young;Kim, Sung-Joo
胰岛移植可以纠正1型糖尿病的异常糖代谢。尽管免疫抑制剂大大降低了移植患者的急性排斥率，但长期副作用可能会使人衰弱。因此，研究人员正在寻求开发新的免疫抑制方案，以诱导最大水平的免疫抑制且副作用较小。迷迭香酸 (Ros A) 是某些草药的次生代谢产物，具有多种生物活性，包括抗炎作用。在这里，我们研究了用 Ros A 和抗 CD154 单克隆抗体 (MR1) 组合治疗小鼠是否可以提高小鼠模型中胰岛同种异体移植物的存活率。移植后，小鼠接受 Ros A、MR1 或两者治疗（“双重”治疗）。与仅接受 Ros A 或 MR1 的动物相比，双重治疗的动物的同种异体移植物存活时间延长。与移植后 15 天接受单一治疗的动物的情况一样，双重治疗的受体并未表现出细胞因子表达或活化 T 细胞群的显着下降。相对于对照组或RosA 组，MR1 或双重治疗组中浸润性CD3(+) T 细胞减少。然而，在同一时间点，与单处理组相比，双处理移植物显示出较少的凋亡细胞以及胰岛素和胰高血糖素的表达增加。此外，与 MR1 处理的移植物相比，接受双重治疗的长期（> 150 天）同种异体移植物表现出更大的胰岛簇，并包含更多的胰岛素和胰高血糖素阳性细胞。总之，Ros A 和 MR1 联合治疗在小鼠胰岛同种移植中具有协同作用。
Pancreatic islet transplantation can correct the abnormal glucose metabolism of Type 1 diabetes. Although immunosuppressants greatly reduce the acute rejection rate in transplant patients, the long-term side effects can be debilitating. Therefore, researchers are seeking to develop new immunosuppressive regimens that induce maximal levels of immunosuppression with minor side effects. Rosmarinic acid (Ros A) is a secondary metabolite of certain herbs and has multiple biological activities, including anti-inflammatory effects. Here, we have investigated whether treatment of mice with a combination of Ros A and anti-CD154 monoclonal antibody (MR1) improves islet allograft survival in a murine model. After transplantation, the mice were treated with either Ros A, MR1, or both (the "double" treatment). Allograft survival was prolonged in the double-treated animals compared to animals that received only Ros A or MR1. As is the case with the single-treated animals at 15 days after transplantation, the double-treated recipients did not display a significant decrease in the expression of cytokines or the population of activated T cells. Infiltrating CD3(+) T cells were reduced in the MR1- or double therapy relative to control or RosA group. However, at the same time point, double-treated graft showed fewer apoptotic cells and increased expression of insulin and glucagons, compared to the single-treatment groups. Furthermore, long-term (> 150 days) allografts that were received with double therapy exhibited larger islet clusters and contained more insulin- and glucagon-positive cells, relative to the MR1-treated grafts. In conclusion, treatment with both Ros A and MR1 has a synergistic effect in murine islet allotransplantation.