Epithelial kinetics in mouse heterotopic tracheal allografts
Epithelial kinetics in mouse heterotopic tracheal allografts
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DOI：
10.1034/j.1600-6143.2002.20503.x
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发表时间：
2002-05-01
影响因子：
8.8
通讯作者：
Randell, SH
中科院分区：
文献类型：
--
作者：
Neuringer, IP;Aris, RM;Randell, SH
闭塞性细支气管炎（OB）是肺移植术后移植物功能障碍的最重要原因。小气道上皮可能是同种免疫反应的靶标，上皮完整性是气道通畅的关键决定因素。我们的目标是阐明异位小鼠气管模型中的上皮细胞动力学，并确定同种异体移植物中细胞死亡的潜在机制。将BALB/c气管分别移植到C57BL/6和BALB/c免疫抑制和非免疫抑制宿主体内，获得同种异体移植物和等异体移植物，于第3-20天收获。进行了形态测定、BrdU和TUNEL标记以及EM研究。同种异体移植物和同种异体移植物的柱状上皮在第0-3天脱落，但在第10天再生。随后，同种异体移植物发生炎症和脱落，而同种异体移植物保留完整的上皮。在气道脱落之前，同种异体移植物表现出明显增加的上皮细胞密度、BrdU标记指数（LI）和TUNEL阳性细胞。电镜下证实上皮细胞凋亡。同种异体纤毛柱状上皮百分率和管腔周长均明显降低。环孢素延缓了气道纤维化，但在同种异体移植物在早期缺血损伤、气道上皮细胞再生和最终细胞死亡阶段的进展过程中没有。这些研究定量地表明，同种异体移植上皮在同种免疫环境中积极再生，但屈服于增加的凋亡呼叫死亡，强调了气道上皮作为异体抗原自我更新来源的重要性。
Obliterative bronchiolitis (OB) is the most important cause of graft dysfunction post-lung transplantation. It is likely that the small airway epithelium is a target of the alloimmune response, and that epithelial Integrity is a crucial determinant of airway patency. Our goals are to elucidate epithelial cell kinetics in the heterotopic mouse trachea model and to determine potential mechanisms of cell death in allografts. Allografts and isografts were obtained by transplanting BALB/c tracheas into C57BL/6 and BALB/c immunosuppressed and non-immunosuppressed hosts, respectively and harvested from day 3-20. Morphometry, BrdU and TUNEL labeling, and EM studies were performed. Columnar epithelium in isografts and allografts sloughs during day 0-3, but regenerates in both sets of grafts by day 10. Subsequently, allografts become inflamed and denuded, while isografts retain an intact epithelium. Prior to airway denudation, allografts exhibited significantly increased epithelial cell density, BrdU labeling index (LI), and TUNEL positive cells. Epithelial apoptosis was confirmed by electron microscopy. Allograft percent ciliated columnar epithelium and lumenal circumference were significantly decreased. Cyclosporin delayed airway fibrosis but did not after the progression of the allograft through the phases of early ischemic Injury, airway epithelial cell regeneration, and eventual cell death. These studies quantitatively demonstrate that the allograft epithelium actively regenerates In the alloimmune environment, but succumbs to Increased apoptotic call death, underscoring the importance of the airway epithelium as a self-renewing source of alloantigen.