Bone marrow production of lung cells: The impact of G-CSF, cardiotoxin, graded doses of irradiation, and subpopulation phenotype

Jason M. Aliotta, Patrick Keaney, Michael Passero, Mark S. Dooner, Jeffrey Pimentel, Deborah Greer, Delia Demers, Bethany Foster, Abigail Peterson, Gerri Dooner, Neil D. Theise, Mehrdad Abedi, Gerald A. Colvin, Peter J. Quesenberry

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)230-241
Number of pages12
JournalExperimental Hematology
Volume34
Issue number2
DOIs
StatePublished - Feb 2006
Externally publishedYes

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Cardiotoxins
Granulocyte Colony-Stimulating Factor
Bone Marrow
Phenotype
Lung
Green Fluorescent Proteins
Radiation
Keratins
Transplantation
Epithelial Cells
Whole-Body Irradiation

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Genetics
  • Hematology
  • Oncology
  • Transplantation

Cite this

Aliotta, J. M., Keaney, P., Passero, M., Dooner, M. S., Pimentel, J., Greer, D., ... Quesenberry, P. J. (2006). Bone marrow production of lung cells: The impact of G-CSF, cardiotoxin, graded doses of irradiation, and subpopulation phenotype. Experimental Hematology, 34(2), 230-241. https://doi.org/10.1016/j.exphem.2005.11.007

Bone marrow production of lung cells : The impact of G-CSF, cardiotoxin, graded doses of irradiation, and subpopulation phenotype. / Aliotta, Jason M.; Keaney, Patrick; Passero, Michael; Dooner, Mark S.; Pimentel, Jeffrey; Greer, Deborah; Demers, Delia; Foster, Bethany; Peterson, Abigail; Dooner, Gerri; Theise, Neil D.; Abedi, Mehrdad; Colvin, Gerald A.; Quesenberry, Peter J.

In: Experimental Hematology, Vol. 34, No. 2, 02.2006, p. 230-241.

Research output: Contribution to journalArticle

Aliotta, JM, Keaney, P, Passero, M, Dooner, MS, Pimentel, J, Greer, D, Demers, D, Foster, B, Peterson, A, Dooner, G, Theise, ND, Abedi, M, Colvin, GA & Quesenberry, PJ 2006, 'Bone marrow production of lung cells: The impact of G-CSF, cardiotoxin, graded doses of irradiation, and subpopulation phenotype', Experimental Hematology, vol. 34, no. 2, pp. 230-241. https://doi.org/10.1016/j.exphem.2005.11.007
Aliotta, Jason M. ; Keaney, Patrick ; Passero, Michael ; Dooner, Mark S. ; Pimentel, Jeffrey ; Greer, Deborah ; Demers, Delia ; Foster, Bethany ; Peterson, Abigail ; Dooner, Gerri ; Theise, Neil D. ; Abedi, Mehrdad ; Colvin, Gerald A. ; Quesenberry, Peter J. / Bone marrow production of lung cells : The impact of G-CSF, cardiotoxin, graded doses of irradiation, and subpopulation phenotype. In: Experimental Hematology. 2006 ; Vol. 34, No. 2. pp. 230-241.
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abstract = "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.",
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AU - Aliotta, Jason M.

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AU - Passero, Michael

AU - Dooner, Mark S.

AU - Pimentel, Jeffrey

AU - Greer, Deborah

AU - Demers, Delia

AU - Foster, Bethany

AU - Peterson, Abigail

AU - Dooner, Gerri

AU - Theise, Neil D.

AU - Abedi, Mehrdad

AU - Colvin, Gerald A.

AU - Quesenberry, Peter J.

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N2 - 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.

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