Yang Min, Chen Gen, Zhang Xue, Ding Zuochuan, Miao Yan, Yang Yang, Chen Zhonghua Klaus, Jiang Fengchao, Chang Sheng, Zhou Ping
Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Key Laboratory of Organ Transplantation, Ministry of Education, NHC Key Laboratory of Organ Transplantation, Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan 43003, China.
Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Transpl Immunol. 2019 Apr;53:1-6. doi: 10.1016/j.trim.2018.11.006. Epub 2018 Nov 22.
After lung transplantation, the major complication limiting the long-term survival of allografts is obliterative bronchiolitis (OB), characterized by chronic rejection. Innate immune responses contribute to the development of OB. In this study, we used a murine heterotopic tracheal transplantation mouse model to examine the effects of a newtype of innate immune inhibitor, TJ-M2010-5.
Syngeneic tracheal grafts were transplanted heterotopically from C57BL/6 mice to C57BL/6 mice. Allografts from BALB/c mice were transplanted to C57BL/6 mice. The allograft recipients were treated with TJ-M2010-5, and anti-mouse CD154 (MR-1). The grafts were harvested at 7, 14, and 28 days and evaluated by histological and real-time RT-PCR analyses.
In untreated allografts, almost all epithelial cells fell off at 7 days and tracheal occlusion reached a peak at 28 days. However, the loss of the epithelium and airway obstruction were significantly improved in mice treated with TJ-M2010-5 combined with MR-1. The relative mRNA expression levels of pro-inflammatory cytokines were upregulated in allogeneic tracheal grafts, and treatment with the two drugs reduced the production of pro-inflammatory cytokines and infiltration of inflammatory cells.
In heterotopic tracheal transplantation models, TJ-M2010-5 combined with MR-1 could ameliorate the development of OB.
肺移植后，限制同种异体移植物长期存活的主要并发症是闭塞性细支气管炎（OB），其特征为慢性排斥反应。固有免疫反应促成了OB的发展。在本研究中，我们使用小鼠异位气管移植模型来研究一种新型固有免疫抑制剂TJ-M2010-5的作用。
将同基因气管移植物从C57BL/6小鼠异位移植到C57BL/6小鼠。将BALB/c小鼠的同种异体移植物移植到C57BL/6小鼠。对同种异体移植物受体用TJ-M2010-5和抗小鼠CD154（MR-1）进行治疗。在第7、14和28天收获移植物，并通过组织学和实时逆转录聚合酶链反应分析进行评估。
在未治疗的同种异体移植物中，几乎所有上皮细胞在第7天脱落，气管闭塞在第28天达到峰值。然而，用TJ-M2010-5联合MR-1治疗的小鼠中，上皮细胞的丧失和气道阻塞得到了显著改善。同种异体气管移植物中促炎细胞因子的相对mRNA表达水平上调，两种药物治疗降低了促炎细胞因子的产生和炎症细胞的浸润。
在异位气管移植模型中，TJ-M2010-5联合MR-1可改善OB的发展。
