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非侵入性同种异体移植急性排斥反应的影像学评估:(131)I-抗 CXCL10 mAb 的评价。

Noninvasive allograft imaging of acute rejection: evaluation of (131)I-anti-CXCL10 mAb.

机构信息

Key Laboratory for Experimental Teratology of the Ministry of Education and Biomedical Isotope Research Center, School of Medicine, Shandong University, 44# Wenhua Xi Road, Jinan, Shandong, 250012, People's Republic of China.

出版信息

Inflammation. 2015 Feb;38(1):456-64. doi: 10.1007/s10753-014-0050-8.

DOI:10.1007/s10753-014-0050-8
PMID:25338944
Abstract

The purpose of this study was to investigate the use of iodine-131-labeled anti-CXCL10 mAb as tracer targeted at CXCL10 to detect acute rejection (AR) with mice model. Expression of CXCL10 was proved by RT-PCR, ELISA, and immunochemistry staining. All groups were submitted to whole-body autoradioimaging and ex vivo biodistribution studies after tail vein injection of (131)I-anti-CXCL10 mAb. The highest concentration/expression of CXCL10 was detected in allograft tissue compared with allograft treated with tacrolimus and isograft control. Tacrolimus could obviously inhibit the rejection of allograft. Allograft could be obviously imaged at all checking points, much clearer than the other two groups. The biodistribution results showed the highest uptake of radiotracer in allograft. T/NT (target/nontarget) ratio was 4.15 ± 0.25 at 72 h, apparently different from allograft treated with tacrolimus (2.29 ± 0.10), P < 0.05. These data suggest that CXCL10 is a promising target for early stage AR imaging and (131)I-CXCL10 mAb can successfully image AR and monitor the effect of immunosuppressant.

摘要

本研究旨在探讨使用碘-131 标记的抗 CXCL10 mAb 作为 CXCL10 的示踪剂,通过小鼠模型检测急性排斥反应(AR)。通过 RT-PCR、ELISA 和免疫化学染色证实 CXCL10 的表达。所有组在尾静脉注射(131)I-抗 CXCL10 mAb 后进行全身放射自显影和离体生物分布研究。与他克莫司处理的同种异体移植物和同种异体对照相比,同种异体移植物组织中检测到 CXCL10 的最高浓度/表达。他克莫司能明显抑制同种异体移植物的排斥反应。在所有检查点,同种异体移植物均可明显成像,明显比其他两组更清晰。生物分布结果显示放射性示踪剂在同种异体移植物中的摄取最高。在 72 小时时,T/NT(靶/非靶)比值为 4.15±0.25,与他克莫司处理的同种异体移植物(2.29±0.10)明显不同,P<0.05。这些数据表明,CXCL10 是早期 AR 成像的有前途的靶点,(131)I-CXCL10 mAb 可成功成像 AR 并监测免疫抑制剂的效果。

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本文引用的文献

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Tacrolimus (FK506) suppresses TNF-α-induced CCL2 (MCP-1) and CXCL10 (IP-10) expression via the inhibition of p38 MAP kinase activation in human colonic myofibroblasts.他克莫司(FK506)通过抑制人结肠肌成纤维细胞中 p38MAP 激酶的激活,抑制 TNF-α 诱导的 CCL2(MCP-1)和 CXCL10(IP-10)的表达。
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血清趋化因子 CXC 配体 10(CXCL10)可预测丙型肝炎感染肝移植后的纤维化进展。
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The Registry of the International Society for Heart and Lung Transplantation: Twenty-sixth Official Adult Lung and Heart-Lung Transplantation Report-2009.国际心肺移植学会登记处:2009年第26份成人肺与心肺移植官方报告
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