Leukocyte-suppressing influences of interleukin (IL)-10 in cardiac allografts: insights from IL-10 knockout mice.
Leukocyte-suppressing influences of interleukin (IL)-10 in cardiac allografts: insights from IL-10 knockout mice.
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白细胞介素 (IL)-10 对心脏同种异体移植物的白细胞抑制影响：来自 IL-10 敲除小鼠的见解。
DOI：
10.1016/s0002-9440(10)65737-9
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Russell,ME
中科院分区：
文献类型：
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作者：
Räisänen-Sokolowski,A;Glysing-Jensen,T;Russell,ME
为了研究白细胞介素(IL)-10在晚期移植物预后中的作用，我们比较了BALB/c供体心脏移植给免疫抑制野生型或IL-10基因缺陷（- / -）C57BL受体（n = 49） 50±5天。IL-10 - / -受体的移植物有明显的白细胞浸润和实质破坏，并有更严重的血管闭塞。在IL-10缺乏的情况下发生闭塞性CD45+动脉炎伴内侧坏死，而不是野生型受体中出现的α-平滑肌肌动蛋白丰富的动脉硬化。通过32p逆转录聚合酶链反应评估，IL-10−/−受体的同种异体移植物中，干扰素(IFN)-γ以及Mac-1、诱导型一氧化氮合酶和异体移植物炎症因子-1（但不包括CD3和IL-4）转录水平升高。然后，我们通过中和IFN-γ来评估IFN-γ介导的反应的贡献。抗IFN-γ单克隆抗体（MAb）治疗IL-10−/−受体并没有改善移植物存活、实质排斥或闭塞性动脉炎，表明这些过程与IFN-γ无关。然而，抗ifn -γ单抗可减轻IL-10−/−受体的内侧平滑肌细胞损失。因此，在移植模型中，IL-10抑制T细胞和巨噬细胞在实质和脉管系统中的反应，并赋予对晚期排斥反应的保护作用。
To investigate the role of interleukin (IL)-10 in late graft outcomes, we compared BALB/c donor hearts transplanted into immunosuppressed wild-type or IL-10 gene-deficient (−/−) C57BL recipients (n = 49) at 50 ± 5 days. There was prominent leukocyte infiltration and parenchymal destruction with more severe vascular occlusion in grafts from IL-10 −/− recipients. An occlusive CD45+arteritis with medial necrosis occurred with IL-10 deficiency instead of the α-smooth muscle actin-rich arteriosclerosis seen in wild-type recipients. Increased interferon (IFN)-γ as well as Mac-1, inducible nitric oxide synthase, and allograft inflammatory factor-1 (but not CD3 and IL-4) transcript levels were seen in allografts from IL-10 −/− recipients as assessed by32P reverse transcription polymerase chain reaction. We then evaluated the contribution of IFN-γ-mediated responses by neutralizing IFN-γ. Anti-IFN-γ monoclonal antibody (MAb) treatment of IL-10 −/− recipients did not improve graft survival, parenchymal rejection, or occlusive arteritis, indicating that these processes are IFN-γ independent. However, medial smooth muscle cell loss in IL-10 −/− recipients was attenuated by anti-IFN-γ MAb. Hence, in this transplant model, IL-10 suppresses T cell and macrophage responses in the parenchyma and vasculature and confers a protective effect against late rejection.