Radiation pneumonitis in mice: a severe injury model for pneumocyte engraftment from bone marrow.
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.
Theise
Neil D
ND
Department of Pathology, New York University School of Medicine, New York, NY 10016, USA. Neil.Theise@med.nyu.edu
Henegariu
Octavian
O
Grove
Joanna
J
Jagirdar
Jayishree
J
Kao
Peter N
PN
Crawford
James M
JM
Badve
Sunil
S
Saxena
Romil
R
Krause
Diane S
DS
D000818:Animals; D015415:Biomarkers; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D019070:Cell Lineage; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D006085:Graft Survival; D017404:In Situ Hybridization, Fluorescence; D008168:Lung / Q000473:pathology* / Q000528:radiation effects; D008297:Male; D051379:Mice; D023421:Models, Animal; D011650:Pulmonary Alveoli / Q000166:cytology; D037701:Pulmonary Surfactant-Associated Protein B / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D011828:Radiation Chimera; D017564:Radiation Pneumonitis / Q000628:therapy*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D014998:Y Chromosome
D015415:Biomarkers; D037701:Pulmonary Surfactant-Associated Protein B; D012333:RNA, Messenger