Repopulation of the irradiation damaged lung with bone marrow-derived cells.
OBJECTIVE
The effect of lung irradiation on reduction of lung stem cells and repopulation with bone marrow-derived cells was measured.


METHODS
Expression of green fluorescent protein positive cells (GFP(+)) in the lungs of thoracic irradiated FVB/NHsd mice (Harlan Sprague Dawley, Indianapolis, IN, USA) was determined. This was compared to the repopulation of bone marrow-derived cells found in the lungs from naphthalene treated male FVB/NHsd mice and gangciclovir (GCV) treated FeVBN GFP(+) male marrow chimeric HSV-TK-CCSP. The level of mRNA for lung stem cell markers clara cell (CCSP), epithelium 1 (FOXJ1) and surfactant protein C (SP-C), and sorted single cells positive for marrow origin epithelial cells (GFP(+)CD45(-)) was measured.


RESULTS
The expression of pulmonary stem cells as determined by PCR was reduced most by GCV, then naphthalene, and least by thoracic irradiation. Irradiation, like GCV, reduced mRNA expression of CCSP, CYP2F2, and FOXJ1, while naphthalene reduced that of CCSP and CYP2F2. Ultrastructural analysis showed GFP(+) pulmonary cells of bone marrow origin, with the highest frequency being found in GCV-treated groups.


CONCLUSIONS
Bone marrow progenitor cells may not participate in the repopulation of the lung following irradiation.
Department of Radiation Oncology, University of Pittsburgh Cancer Institute, 5150 Centre Avenue, Pittsburgh, PA 15232, USA.
Mark E
ME
Bernard
Hyun
H
Kim
Malolan S
MS
Rajagopalan
Brandon
B
Stone
Umar
U
Salimi
Jean-Claude
JC
Rwigema
Michael W
MW
Epperly
Hongmei
H
Shen
Julie P
JP
Goff
Darcy
D
Franicola
Tracy
T
Dixon
Shaonan
S
Cao
Xichen
X
Zhang
Hong
H
Wang
Donna B
DB
Stolz
Joel S
JS
Greenberger
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000378:metabolism* / Q000648:ultrastructure; D016026:Bone Marrow Transplantation / Q000379:methods*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D004847:Epithelial Cells / Q000378:metabolism* / Q000648:ultrastructure; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics; D015774:Ganciclovir / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects / Q000528:radiation effects; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D009281:Naphthalenes / Q000494:pharmacology; D037721:Pulmonary Surfactant-Associated Protein C / Q000235:genetics; D011833:Radiation Injuries, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014598:Uteroglobin / Q000235:genetics
D000998:Antiviral Agents; C481963:FOXJ1 protein, mouse; D051858:Forkhead Transcription Factors; D009281:Naphthalenes; D037721:Pulmonary Surfactant-Associated Protein C; C556390:Scgb1a1 protein, mouse; D049452:Green Fluorescent Proteins; C031721:naphthalene; D003577:Cytochrome P-450 Enzyme System; D014598:Uteroglobin; C110333:Cyp2f2 protein, mouse; D015774:Ganciclovir