Radiation pneumonitis in mice: a severe injury model for pneumocyte engraftment from bone marrow

Exp Hematol. 2002 Nov;30(11):1333-8. doi: 10.1016/s0301-472x(02)00931-1.


Objective: To better understand the process by which pneumocytes can be derived from bone marrow cells, we investigated the in vivo kinetics of such engraftment following lethal irradiation.

Methods: A cohort of lethally irradiated B6D2F1 female mice received whole bone marrow transplants (BMT) from age-matched male donors and were sacrificed at days 1, 3, 5, and 7 and months 2, 4, and 6 post-BMT (n = 3 for each time point). Additionally, 2 female mice who had received 200 male fluorescence-activated cell sorter (FACS)-sorted CD34(+)lin(-) cells were sacrificed 8 months post-BMT.

Results: Lethal irradiation caused histologic evidence of pneumonitis including alveolar breakdown and hemorrhage beginning at day 3. To identify male-derived pneumocytes, simultaneous fluorescence in situ hybridization (FISH) for Y-chromosome and surfactant B messenger RNA was performed on lung tissue. Y(+) type II pneumocytes were engrafted as early as day 5 posttransplant, and eventually from 2 to 14% of the pneumocytes were donor derived in individual mice. Co-staining for epithelial-specific cytokeratins demonstrated that by 2 months, marrow-derived pneumocytes could comprise entire alveoli, suggesting that type I cells derived from type II pneumocytes.

Conclusions: We conclude that alveolar lining cells derive from bone marrow cells immediately after acute injury. Also, the CD34(+)lin(-) subpopulation is capable of such pulmonary engraftment.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Biomarkers
  • Bone Marrow Transplantation*
  • Cell Differentiation
  • Cell Lineage*
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism
  • Female
  • Graft Survival
  • In Situ Hybridization, Fluorescence
  • Lung / pathology*
  • Lung / radiation effects
  • Male
  • Mice
  • Models, Animal
  • Pulmonary Alveoli / cytology
  • Pulmonary Surfactant-Associated Protein B / genetics
  • RNA, Messenger / analysis
  • Radiation Chimera
  • Radiation Pneumonitis / therapy*
  • Stem Cell Transplantation*
  • Stem Cells / cytology
  • Stem Cells / metabolism
  • Y Chromosome


  • Biomarkers
  • Pulmonary Surfactant-Associated Protein B
  • RNA, Messenger