title: Radiation pneumonitis in mice: a severe injury model for pneumocyte engraftment from bone marrow.
abstract: 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.
authors.affiliation: Department of Pathology, New York University School of Medicine, New York, NY 10016, USA. Neil.Theise@med.nyu.edu
authors.forename: Neil D
authors.initials: ND
authors.lastname: Theise
authors.forename: Octavian
authors.initials: O
authors.lastname: Henegariu
authors.forename: Joanna
authors.initials: J
authors.lastname: Grove
authors.forename: Jayishree
authors.initials: J
authors.lastname: Jagirdar
authors.forename: Peter N
authors.initials: PN
authors.lastname: Kao
authors.forename: James M
authors.initials: JM
authors.lastname: Crawford
authors.forename: Sunil
authors.initials: S
authors.lastname: Badve
authors.forename: Romil
authors.initials: R
authors.lastname: Saxena
authors.forename: Diane S
authors.initials: DS
authors.lastname: Krause
mesh_terms: 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
chemical_list: D015415:Biomarkers; D037701:Pulmonary Surfactant-Associated Protein B; D012333:RNA, Messenger