PMID- 12423687 OWN - NLM STAT- MEDLINE DCOM- 20021212 LR - 20191025 IS - 0301-472X (Print) IS - 0301-472X (Linking) VI - 30 IP - 11 DP - 2002 Nov TI - Radiation pneumonitis in mice: a severe injury model for pneumocyte engraftment from bone marrow. PG - 1333-8 AB - 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. FAU - Theise, Neil D AU - Theise ND AD - Department of Pathology, New York University School of Medicine, New York, NY 10016, USA. Neil.Theise@med.nyu.edu FAU - Henegariu, Octavian AU - Henegariu O FAU - Grove, Joanna AU - Grove J FAU - Jagirdar, Jayishree AU - Jagirdar J FAU - Kao, Peter N AU - Kao PN FAU - Crawford, James M AU - Crawford JM FAU - Badve, Sunil AU - Badve S FAU - Saxena, Romil AU - Saxena R FAU - Krause, Diane S AU - Krause DS LA - eng GR - DK53037/DK/NIDDK NIH HHS/United States GR - HK69207/HK/PHITPO CDC HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - Netherlands TA - Exp Hematol JT - Experimental hematology JID - 0402313 RN - 0 (Biomarkers) RN - 0 (Pulmonary Surfactant-Associated Protein B) RN - 0 (RNA, Messenger) SB - IM MH - Animals MH - Biomarkers MH - *Bone Marrow Transplantation MH - Cell Differentiation MH - *Cell Lineage MH - Epithelial Cells/cytology/metabolism MH - Female MH - Graft Survival MH - In Situ Hybridization, Fluorescence MH - Lung/*pathology/radiation effects MH - Male MH - Mice MH - Models, Animal MH - Pulmonary Alveoli/cytology MH - Pulmonary Surfactant-Associated Protein B/genetics MH - RNA, Messenger/analysis MH - Radiation Chimera MH - Radiation Pneumonitis/*therapy MH - *Stem Cell Transplantation MH - Stem Cells/cytology/metabolism MH - Y Chromosome EDAT- 2002/11/09 04:00 MHDA- 2002/12/13 04:00 CRDT- 2002/11/09 04:00 PHST- 2002/11/09 04:00 [pubmed] PHST- 2002/12/13 04:00 [medline] PHST- 2002/11/09 04:00 [entrez] AID - S0301472X02009311 [pii] AID - 10.1016/s0301-472x(02)00931-1 [doi] PST - ppublish SO - Exp Hematol. 2002 Nov;30(11):1333-8. doi: 10.1016/s0301-472x(02)00931-1.