Radiation pneumonitis in mice: A severe injury model for pneumocyte engraftment from bone marrow

Radiation pneumonitis in mice: A severe injury model for pneumocyte engraftment from bone marrow
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DOI:
10.1016/s0301-472x(02)00931-1
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发表时间:
2002-11-01
影响因子:
2.6
通讯作者:
Krause, DS
Krause, DS
中科院分区:
医学4区
文献类型:
--
作者:
Theise, ND;Henegariu, O;Krause, DS

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Objective.为了更好地理解肺细胞可以从骨髓细胞衍生的过程,我们研究了致死辐射后这种植入的体内动力学。一组致死剂量照射的B6 D2 F1雌性小鼠接受来自年龄匹配的雄性供体的全骨髓移植(BMT),并在BMT后第1、3、5和7天以及第2、4和6个月处死(每个时间点n = 3)。另外,接受200只雄性荧光激活细胞分选仪(FACS)分选的CD 34(+)lin(-)细胞的2只雌性小鼠在BMT后8个月处死。致死性照射引起肺部炎症的组织学证据,包括肺泡破裂和出血,从第3天开始。为了鉴定男性来源的肺细胞,对肺组织进行Y染色体和表面活性剂B信使RNA的同步荧光原位杂交(FISH)。早在移植后第5天,Y+ H型肺细胞就被移植,最终在个体小鼠中有2 - 14%的肺细胞是供体来源的。上皮特异性细胞角蛋白的共染色显示,在2个月时,骨髓来源的肺细胞可以包含整个肺泡,提示I型细胞来源于H型肺细胞。我们的结论是,肺泡衬里细胞来源于骨髓细胞急性损伤后立即。此外,CD 34(+)lin(-)亚群能够进行这种肺植入。(C)2002年国际实验血液学学会。出版社:Elsevier Science Inc.
Objective. To better understand the process by which pneumocytes can be derived from bone marrow cells, we investigated the in vivo kinetics of such engraftment following lethal irradiation.Methods. A cohort of lethally irradiated B6D2F1 female mice received whole bone marrow transplants (BMT) from age-matched male donors and were sacrificed at days 1, 3, 5, and 7 and months 2,4, and 6 post-BMT (n = 3 for each time point). Additionally, 2 female mice who had received 200 male fluorescence-activated cell sorter (FACS)-sorted CD34(+)lin(-) cells were sacrificed 8 months post-BMT.Results. Lethal irradiation caused histologic evidence of pneumonitis including alveolar breakdown and hemorrhage beginning at day 3. To identify male-derived pneumocytes, simultaneous fluorescence in situ hybridization (FISH) for Y-chromosome and surfactant B messenger RNA was performed on lung tissue. Y+ type H pneumocytes were engrafted as early as day 5 posttransplant, and eventually from 2 to 14% of the pneumocytes were donor derived in individual mice. Co-staining for epithelial-specific cytokeratins demonstrated that by 2 months, marrow-derived pneumocytes could comprise entire alveoli, suggesting that type I cells derived from type H pneumocytes.Conclusion. We conclude that alveolar lining cells derive from bone marrow cells immediately after acute injury. Also, the CD34(+)lin(-) subpopulation is capable of such pulmonary engraftment. (C) 2002 International Society for Experimental Hematology. Published by Elsevier Science Inc.