Bone marrow production of lung cells: The impact of G-CSF, cardiotoxin, graded doses of irradiation, and subpopulation phenotype
Bone marrow production of lung cells: The impact of G-CSF, cardiotoxin, graded doses of irradiation, and subpopulation phenotype
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DOI：
10.1016/j.exphem.2005.11.007
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发表时间：
2006-02-01
影响因子：
2.6
通讯作者：
Quesenberry, PJ
中科院分区：
文献类型：
--
作者：
Aliotta, JM;Keaney, P;Quesenberry, PJ
目标。以前的研究已经证明，在不同的实验条件下，骨髓细胞可以产生各种类型的肺细胞。我们的目的是确定影响肺部转化的一些变量。在单独的实验中，小鼠接受不同剂量的全身照射，然后移植来自GFP(+) （C57BL/6-TgN[ACTbEGFP]1Osb）小鼠的整个骨髓或各种骨髓亚群(Lin(-/+), c-kit（-/+), Sca-1(-/+)）。部分患者给予心肌毒素和/或粒细胞集落刺激因子（G-CSF）动员。利用绿色荧光蛋白（GFP）抗体标记来排除自身荧光和反褶积显微镜来确定移植后肺样本中GFP和细胞角蛋白的共定位以及CD45的缺失，建立了移植骨髓中肺上皮细胞的产生。随着放射剂量的增加，更多的供体来源的肺细胞(GFP（+)/CD45(-)）出现（5.43%的肺细胞，1200 cGy）。在900-cGy组中，61.43%的GFP(+)/CD45（-）细胞也是细胞角蛋白（+）。在辐射损伤小鼠中，动员进一步使GFP(+)/CD45（-）细胞增加到7.88%。在移植了Lin（-）、c-kit（+）或Sca-1（+）骨髓细胞的辐射损伤小鼠中，高达1.67%的肺细胞是GFP(+)/CD45（-）。Lin（+）亚群、c-kit（-）亚群和Sca-1（-）亚群对肺移植无显著影响。我们已经确定骨髓细胞能够产生肺上皮细胞，并确定辐射剂量和G-CSF动员是影响骨髓细胞产生肺细胞的变量。此外，假定的肺细胞生成骨髓细胞具有造血干细胞的表型。(C) 2006国际实验血液学学会。Elsevier Inc.出版。
Objective. Previous studies have demonstrated the production of various types of lung cells from marrow cells under diverse experimental conditions. Our aim was to identify some of the variables that influence conversion in the lung.Methods. In separate experiments, mice received various doses of total-body irradiation followed by transplantation with whole bone marrow or various subpopulations of marrow cells (Lin(-/+), c-kit(-/+), Sca-1(-/+)) from GFP(+) (C57BL/6-TgN[ACTbEGFP]1Osb) mice. Some were given intramuscular cardiotoxin and/or mobilized with granulocyte colony-stimulating factor (G-CSF).Results. The production of pulmonary epithelial cells from engrafted bone marrow was established utilizing green fluorescent protein (GFP) antibody labeling to rule out autofluorescence and deconvolution microscopy to establish the colocaliztion of GFP and cytokeratin and the absence of CD45 in lung samples after transplantation. More donor-derived lung cells (GFP(+)/CD45(-)) were seen with increasing doses of radiation (5.43% of all lung cells, 1200 cGy). In the 900-cGy group, 61.43% of GFP(+)/CD45(-) cells were also cytokeratin(+). Mobilization further increased GFP(+)/CD45(-) cells to 7.88% in radiation-injured mice. Up to 1.67% of lung cells were GFP(+)/CD45(-) in radiation-injured mice transplanted with Lin(-), c-kit(+), or Sca-1(+) marrow cells. Lin(+), c-kit(-), and Sca-1(-) subpopulations did not significantly engraft the lung.Conclusions. We have established that marrow cells are capable of producing pulmonary epithelial cells and identified radiation dose and G-CSF mobilization as variables influencing the production of lung cells from marrow cells. Furthermore, the putative lung cell-producing marrow cell has the phenotype of a hematopoietic stem cell. (C) 2006 International Society for Experimental Hematology. Published by Elsevier Inc.