Fibroblasts of recipient bronchiolitis obliterans origin contribute to in human lung transplants
Fibroblasts of recipient bronchiolitis obliterans origin contribute to in human lung transplants
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DOI：
10.1164/rccm.200509-1381oc
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发表时间：
2006-06-01
影响因子：
24.7
通讯作者：
Lehmann, Ulrich
中科院分区：
文献类型：
--
作者：
Broecker, Verena;Laenger, Florian;Lehmann, Ulrich
基本原理：循环前体细胞参与小鼠实验性肺纤维化病变的发展最近已被证实。目的：本研究分析循环、骨髓来源的成纤维细胞前体细胞是否有助于人肺纤维化病变的发展，特别是闭塞性细支气管炎。方法：人同种异体肺移植物（n = 12）和骨髓移植后患者自体肺组织（n = 2）闭塞性细支气管炎病变中原位微嵌合体的发生免疫组化标记白细胞后，采用激光辅助显微切割进行分析，然后进行基于短串联重复序列-聚合酶链反应的基因分型。联合免疫荧光和荧光原位杂交的性染色体进行了独立的确认，在适当的性别不匹配的情况下（n = 2）。测量和主要结果：闭塞性细支气管炎病变的所有12例肺移植患者含有相当数量的原发性成纤维细胞（平均值，32%）。两名骨髓移植患者的纤维化肺病变也显示出明显的原位微嵌合体。原位检测方法证实了这些结果，虽然程度较低（6-16%）。结论：这些数据清楚地表明参与循环成纤维细胞前体细胞在人类纤维化肺病变的发展，并提供证据表明，这些细胞是最有可能的骨髓来源。这些结果可能为预防肺移植和其他器官中的纤维化开辟新的途径。
Rationale: The participation of circulating precursor cells in the development of experimental pulmonary fibrosing lesions in mice has been recently demonstrated.Objectives: This study analyzes whether circulating, bone marrow-derived, fibroblastic precursor cells contribute to the development of fibrosing lesions in human lungs, especially bronchiolitis obliterans.Methods: The occurrence of in situ microchimerism in bronchiolitis obliterans lesions of human lung allografts (n = 12) as well as of autologous lung tissue from patients post-bone marrow transplantation (n = 2) was analyzed using laser-assisted microdissection after immunohistochemical labeling of leukocytes followed by short tandem repeat-polymerase chain reaction-based genotyping. Combined immunofluorescence and fluorescence in situ hybridization for sex chromosomes was performed for independent confirmation in cases with appropriate sex mismatch (n = 2).Measurements and Main Results: The bronchiolitis obliterans lesions of all 12 lung transplant patients contained considerable numbers of recipient-derived fibroblasts (mean, 32%). The fibrosing pulmonary lesions of the two bone marrow-transplanted patients also displayed clear in situ microchimerism. The in situ detection methodology confirmed these results, although to a lower degree (6-16%).Conclusions: These data clearly demonstrate the involvement of circulating fibroblastic precursor cells in the development of human fibrosing lung lesions and provide evidence that these cells are most probably bone marrow derived. These results may open new venues regarding the prevention of fibrosis in lung transplants and potentially in other organs.