Chronic rejection pathology after orthotopic lung transplantation in mice: the development of a murine BOS model and its drawbacks.
Chronic rejection pathology after orthotopic lung transplantation in mice: the development of a murine BOS model and its drawbacks.
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DOI：
10.1371/journal.pone.0029802
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Vanaudenaerde B
中科院分区：
文献类型：
--
作者：
De Vleeschauwer S;Jungraithmayr W;Wauters S;Willems S;Rinaldi M;Vaneylen A;Verleden S;Willems-Widyastuti A;Bracke K;Brusselle G;Verbeken E;Van Raemdonck D;Verleden G;Vanaudenaerde B
几乎所有的肺移植（LTx）后慢性排斥反应（CR）的动物模型都不能类似于人类的情况。这是我们试图在小鼠中开发CR的代表性模型。在接受类固醇和环孢素每日免疫抑制的同种异体移植物中进行原位LTx。对照组包括同种移植物和仅接受胸廓切开术的小鼠（SHAM）。LTx后2、4、6、8、10或12周处死同种异体移植物。在12周的同种异体移植物、同系移植物和SHAM小鼠中重复测量肺功能。组织学上，所有同种异体移植物在LTx后两周表现出血管和气道周围的急性排斥反应（AR）。10周内下降至50-75%，12周后消失。从4-12周在25-50%的小鼠中观察到闭塞性细支气管炎（OB）病变。12周后，SHAM小鼠的同种移植物和肺均正常。肺功能测定显示术后（2周）FEV0.1、TLC和同种异体移植物顺应性下降，随时间推移恢复缓慢。在这种最初的下降之后，同种异体移植物的肺功能比同种异体移植物和SHAM小鼠增加更多，表明肺功能测量不是诊断小鼠CR的良好工具。我们的结论是，一个真正的模型CR，明确OB病变，在约三分之一的动物，但没有下降的肺功能，是可能的。该模型是CR理想模型开发的重要一步，将为阐明CR发病机制和探索新的治疗方案开辟新的视角。
Almost all animal models for chronic rejection (CR) after lung transplantation (LTx) fail to resemble the human situation. It was our attempt to develop a representative model of CR in mice. Orthotopic LTx was performed in allografts receiving daily immunosuppression with steroids and cyclosporine. Controls included isografts and mice only undergoing thoracotomy (SHAM). Allografts were sacrificed 2, 4, 6, 8, 10 or 12 weeks after LTx. Pulmonary function was measured repeatedly in the 12w allografts, isografts and SHAM mice. Histologically, all allografts demonstrated acute rejection (AR) around the blood vessels and airways two weeks after LTx. This decreased to 50–75% up to 10 weeks and was absent after 12 weeks. Obliterative bronchiolitis (OB) lesions were observed in 25–50% of the mice from 4–12 weeks. Isografts and lungs of SHAM mice were normal after 12 weeks. Pulmonary function measurements showed a decline in FEV0.1, TLC and compliance in the allografts postoperatively (2 weeks) with a slow recovery over time. After this initial decline, lung function of allografts increased more than in isografts and SHAM mice indicating that pulmonary function measurement is not a good tool to diagnose CR in a mouse. We conclude that a true model for CR, with clear OB lesions in about one third of the animals, but without a decline in lung function, is possible. This model is an important step forward in the development of an ideal model for CR which will open new perspectives in unraveling CR pathogenesis and exploring new treatment options.
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影响因子：
24.3
作者：
Jungraithmayr, W.;Vogt, P.;Weder, W.
通讯作者：
Weder, W.
影响因子：
5
作者：
Svetlecic, J;Molteni, A;Herndon, B
通讯作者：
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影响因子：
4.4
作者：
Gelman, Andrew E.;Okazaki, Mikio;Kreisel, Daniel
通讯作者：
Kreisel, Daniel
DOI：
10.1165/rcmb.2007-0257rc
发表时间：
2007-12-01
影响因子：
6.4
作者：
Okazaki, Mikio;Gelman, Andrew E.;Kreisel, Daniel
通讯作者：
Kreisel, Daniel
DOI：
10.1164/rccm.200706-951oc
发表时间：
2008-05-01
影响因子：
24.7
作者：
Glanville, Allan R.;Aboyoun, Christina L.;Malouf, Monique A.
通讯作者：
Malouf, Monique A.