Obliterative airway disease progresses in heterotopic airway allografts without persistent alloimmune stimulus.
Obliterative airway disease progresses in heterotopic airway allografts without persistent alloimmune stimulus.
复制标题
闭塞性气道疾病在异位气道同种异体移植物中进展，无需持续的同种免疫刺激。
DOI：
10.1097/00007890-200208270-00022
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发表时间：
2002
期刊：
影响因子：
6.2
通讯作者：
Hertz,MarshallI
中科院分区：
文献类型：
--
作者：
King,MelissaB;Pedtke,AndrewC;Levrey-Hadden,HeleneL;Hertz,MarshallI
背景：高达50%的人肺移植发生慢性排斥反应，表现为闭塞性毛细支气管炎(OB)。尽管受到最大程度的免疫抑制，这种并发症仍经常进展，这表明，一旦启动，除同种异体免疫之外的其他因素在其进展中发挥作用。在动物中，异位移植的同种异体气道会发展为闭塞型呼吸道疾病(OAD)，这是一种免疫介导的病变，被用作OB的临床前模型。我们试图确定即使在移除同种异体免疫环境后，OAD是否会进展。方法：将Lewis大鼠的气管移植到Brown挪威受体的皮下以创建同种异体移植物。在7天或14天的同种异体免疫刺激后，将这些同种异体移植物取出并重新移植到同种环境中，再移植21天。在每个时间点对组织学进行评估，并对气道上皮和管腔内纤维增殖进行定量。结果：与仅暴露7天的移植物相比，接受14天同种异体免疫刺激的同种异体移植物有显著的气道上皮丢失(P<；0.001)。在这两组患者中，几乎没有发现纤维增生。在再次移植后，最初暴露于同种异体免疫刺激7天的移植物几乎没有异常。相反，最初暴露于同种异体免疫14天并再次移植的组腔几乎完全闭塞，伴有纤维增生(96.9%闭塞，P=0.001)和无呼吸道上皮。结论：如果同种异体免疫损伤的初始阶段足够，尽管同种异体免疫被移除，OAD仍会进展。气道上皮细胞丢失与纤维化进展相关，提示上皮细胞在OB的发病机制中起重要作用。
Background.Up to 50% of human lung allografts develop chronic rejection manifested as obliterative bronchiolitis (OB). This complication frequently progresses despite maximal immunosuppression, suggesting that, once initiated, factors other than alloimmunity play a role in its progression. In animals, heterotopically transplanted allograft airways develop obliterative airway disease (OAD), an immunologically mediated lesion that is used as a preclinical model of OB. We sought to determine whether OAD would progress even after removal from the alloimmune environment.Methods.Tracheas from Lewis rats were transplanted subcutaneously into Brown Norway recipients to create allografts. After 7 or 14 days of alloimmune stimulus, these allografts were removed and retransplanted into an isogeneic environment for an additional 21 days. Histology was assessed at each time point, with quantitation of the airway epithelium and intraluminal fibroproliferation.Results.Allografts exposed to 14 days of alloimmune stimulus had a significant loss of airway epithelium compared with grafts exposed to only 7 days (P< 0.001). There was little fibroproliferation seen in either of these groups. After retransplantation, the grafts initially exposed to 7 days of alloimmune stimulus had few abnormalities. In contrast, the group exposed initially to 14 days of alloimmunity and retransplanted had near complete obliteration of the lumen with fibroproliferation (96.9% occlusion, P= 0.001) and absent airway epithelium.Conclusions.OAD progresses despite removal of alloimmunity if the initial period of alloimmune injury is sufficient. Airway epithelial loss correlated with progression to fibroproliferation, suggesting that the epithelium plays a significant role in the pathogenesis of OB.