title: Bone marrow production of lung cells: the impact of G-CSF, cardiotoxin, graded doses of irradiation, and subpopulation phenotype.
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.
authors.affiliation: Roger Williams Medical Center, Center for Stem Cell Biology, Providence, RI 02908, USA. jason.aliotta@verizon.net
authors.forename: Jason M
authors.initials: JM
authors.lastname: Aliotta
authors.forename: Patrick
authors.initials: P
authors.lastname: Keaney
authors.forename: Michael
authors.initials: M
authors.lastname: Passero
authors.forename: Mark S
authors.initials: MS
authors.lastname: Dooner
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Pimentel
authors.forename: Deborah
authors.initials: D
authors.lastname: Greer
authors.forename: Delia
authors.initials: D
authors.lastname: Demers
authors.forename: Bethany
authors.initials: B
authors.lastname: Foster
authors.forename: Abigail
authors.initials: A
authors.lastname: Peterson
authors.forename: Gerri
authors.initials: G
authors.lastname: Dooner
authors.forename: Neil D
authors.initials: ND
authors.lastname: Theise
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Abedi
authors.forename: Gerald A
authors.initials: GA
authors.lastname: Colvin
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Quesenberry
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation / Q000187:drug effects / Q000528:radiation effects; D004179:Cobra Cardiotoxin Proteins / Q000008:administration & dosage*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005451:Fluorescein Angiography; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007273:Injections, Intramuscular; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D014916:Whole-Body Irradiation
chemical_list: D004179:Cobra Cardiotoxin Proteins; D016179:Granulocyte Colony-Stimulating Factor; D049452:Green Fluorescent Proteins