Bröcker Verena, Lehmann Ulrich, Länger Florian, Fellous Tariq G, Mengel Michael, Brittan Mairi, Bredt Martin, Milde Simone, Welte Tobias, Eder Matthias, Haverich Axel, Alison Malcolm R, Kreipe Hans
Institut für Pathologie, Medizinische Hochschule, Hannover.
Verh Dtsch Ges Pathol. 2006;90:277-85.
The participation of circulating precursor cells in the development of experimental pulmonary fibrosing lesions in mice has been recently demonstrated.
This study analyzes whether circulating, bone marrow-derived fibroblastic precursor cells contribute to the development of fibrosing lesions in human lungs, especially bronchiolitis obliterans.
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 STR-PCR-based genotyping. Combined immunofluorescence and fluorescence in situ hybridization for sex chromsomes was performed for independent confirmation in cases with appropriate sex mismatch (n = 2).
The bronchiolitis obliterans lesions of all twelve lung transplant patients contained considerable numbers of recipient-derived fibroblasts (mean: 32 %). The fibrosing pulmonary lesions of the two bone marrow-transplanted patients displayed also clear in situ-microchimerism. The in situ detection methodology confirmed these results, although to a lower degree (6-16%).
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 other organs.
最近已证实在小鼠实验性肺纤维化病变的发展过程中有循环前体细胞参与。
本研究分析循环的、骨髓来源的成纤维细胞前体细胞是否参与人类肺部纤维化病变的发展，尤其是闭塞性细支气管炎。
在对白细胞进行免疫组织化学标记后，使用激光辅助显微切割，然后基于STR-PCR进行基因分型，分析人肺移植（n = 12）闭塞性细支气管炎病变以及骨髓移植后患者（n = 2）自体肺组织中是否存在原位微嵌合体。对于性别不匹配的合适病例（n = 2），进行联合免疫荧光和性染色体荧光原位杂交以进行独立验证。
所有12例肺移植患者的闭塞性细支气管炎病变中都含有大量受体来源的成纤维细胞（平均：32%）。两名骨髓移植患者的纤维化肺部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，尽管程度较低（6 - 16%）。
这些数据清楚地证明了循环成纤维细胞前体细胞参与人类纤维化肺部病变的发展，并提供证据表明这些细胞很可能来自骨髓。这些结果可能为肺移植及其他潜在器官纤维化的预防开辟新途径。
