Bröcker Verena, Länger Florian, Fellous Tariq G, Mengel Michael, Brittan Mairi, Bredt Martin, Milde Simone, Welte Tobias, Eder Matthias, Haverich Axel, Alison Malcolm R, Kreipe Hans, Lehmann Ulrich
Institute of Pathology, Department of Pneumology, Medizinische Hochschule Hannover, Hannover, Germany.
Am J Respir Crit Care Med. 2006 Jun 1;173(11):1276-82. doi: 10.1164/rccm.200509-1381OC. Epub 2006 Mar 9.
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 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).
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%).
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.
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化标记后，采用激光辅助显微切割技术，接着基于短串联重复序列-聚合酶链反应进行基因分型，分析人类肺移植同种异体移植物（n = 12）以及骨髓移植患者的自体肺组织（n = 2）中闭塞性细支气管炎病变中原位微嵌合体的发生情况。对于性别不匹配的合适病例（n = 2），进行性染色体的联合免疫荧光和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均含有大量受体来源的成纤维细胞（平均为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%）。
这些数据清楚地表明循环成纤维细胞前体细胞参与了人类纤维化肺病变的发展，并提供证据表明这些细胞很可能来源于骨髓。这些结果可能为肺移植以及其他器官纤维化的预防开辟新的途径。
