Repopulation of the irradiation damaged lung with bone marrow-derived cells

In Vivo. 2012 Jan-Feb;26(1):9-18.

Abstract

Aim: The effect of lung irradiation on reduction of lung stem cells and repopulation with bone marrow-derived cells was measured.

Materials and 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.

Conclusion: Bone marrow progenitor cells may not participate in the repopulation of the lung following irradiation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antiviral Agents / pharmacology
  • Bone Marrow Cells / metabolism*
  • Bone Marrow Cells / ultrastructure
  • Bone Marrow Transplantation / methods*
  • Cytochrome P-450 Enzyme System / genetics
  • Epithelial Cells / metabolism*
  • Epithelial Cells / ultrastructure
  • Female
  • Forkhead Transcription Factors / genetics
  • Ganciclovir / pharmacology
  • Gene Expression / drug effects
  • Gene Expression / radiation effects
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Lung / drug effects
  • Lung / metabolism*
  • Lung / radiation effects
  • Male
  • Mice
  • Mice, Transgenic
  • Microscopy, Confocal
  • Microscopy, Electron, Transmission
  • Naphthalenes / pharmacology
  • Pulmonary Surfactant-Associated Protein C / genetics
  • Radiation Injuries, Experimental / genetics
  • Radiation Injuries, Experimental / metabolism
  • Radiation Injuries, Experimental / pathology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Uteroglobin / genetics

Substances

  • Antiviral Agents
  • FOXJ1 protein, mouse
  • Forkhead Transcription Factors
  • Naphthalenes
  • Pulmonary Surfactant-Associated Protein C
  • Scgb1a1 protein, mouse
  • Green Fluorescent Proteins
  • naphthalene
  • Cytochrome P-450 Enzyme System
  • Uteroglobin
  • Cyp2f2 protein, mouse
  • Ganciclovir