Effect of CTLA4-Ig on Obliterative Bronchiolitis in a Mouse Intrapulmonary Tracheal Transplantation Model.
Effect of CTLA4-Ig on Obliterative Bronchiolitis in a Mouse Intrapulmonary Tracheal Transplantation Model.
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DOI：
10.5761/atcs.oa.20-00398
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发表时间：
2021-12-20
期刊：
影响因子：
--
通讯作者：
Okada Y
中科院分区：
文献类型：
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作者：
Suzuki Y;Oishi H;Kanehira M;Matsuda Y;Hirama T;Noda M;Okada Y
目的：肺移植术后的严重问题之一是慢性同种异体肺功能障碍（chronic lung allograft dysfunction， CLAD）。大多数CLAD患者的病理特征为闭塞性细支气管炎（OB）。细胞毒性t淋巴细胞相关抗原4 (CTLA4)-Ig是人IgG1 Fc片段与CTLA4细胞外结构域连接的组合蛋白。本研究的目的是通过小鼠肺内气管移植（IPTT）模型研究CTLA4-Ig治疗对OB的影响。方法：对BALB/c（供体）和C57BL/6（受体）小鼠进行IPTT实验。Abatacept是一种市售形式的CTLA4-Ig，在手术后第7、14和21天立即腹腔注射给受体小鼠。对照组小鼠注射人IgG。结果：我们在移植后28天进行了半定量分析。我们计算了每例移植气管管腔的闭塞率。CTLA4-Ig组的闭塞率明显低于对照组（91.2±2.1%比47.8±7.9%,p = 0.0008）。免疫荧光染色显示肺淋巴样细胞新生明显减少。结论：CTLA4-Ig治疗可减轻IPTT模型小鼠纤维组织气管闭塞。纤维闭塞的减弱与淋巴细胞新生的抑制有关。
Objectives: One of the serious problems after lung transplantation is chronic lung allograft dysfunction (CLAD). Most CLAD patients pathologically characterized by obliterative bronchiolitis (OB). Cytotoxic T-lymphocyte-associated antigen 4 (CTLA4)-Ig is a combination protein of the Fc fragment of human IgG1 linked to the extracellular domain of CTLA4. The aim of the study was to examine the effect of CTLA4-Ig therapy on OB using a mouse intrapulmonary tracheal transplantation (IPTT) model. Methods: IPTT was performed between BALB/c (donor) and C57BL/6 (recipient) mice. Abatacept, which is a commercially available form of CTLA4-Ig, was intraperitoneally injected in recipient mice immediately after surgery, on days 7, 14, and 21. The mice in the control group received human IgG. Results: We performed semi-quantitative analysis of graft luminal obliteration at post-transplant day 28. We calculated the obliteration ratio of the lumen of the transplanted trachea in each case. The obliteration ratio was significantly lower in the CTLA4-Ig group than that in the control group (91.2 ± 2.1% vs. 47.8 ± 7.9%, p = 0.0008). Immunofluorescent staining revealed significantly decreased lymphoid neogenesis in the lung. Conclusions: CTLA4-Ig therapy attenuated tracheal obliteration with fibrous tissue in the mouse IPTT model. The attenuation of fibrous obliteration was correlated with the inhibition of lymphoid neogenesis.