Abstract
Bone marrow-derived cells (BMDC) have been shown to graft injured tissues, differentiate in specialized cells, and participate in repair. The importance of these processes in acute lung bacterial inflammation and development of fibrosis is unknown. The goal of this study was to investigate the temporal sequence and lineage commitment of BMDC in mouse lungs injured by bacterial pneumonia. We transplanted GFP-tagged BMDC into 5-Gy-irradiated C57BL/6 mice. After 3 months of recovery, mice were subjected to LD50 intratracheal instillation of live E. coli (controls received saline) which produced pneumonia and subsequent areas of fibrosis. Lungs were investigated by immunohistology for up to 6 months. At the peak of lung inflammation, the predominant influx of BMDC were GFP+ leukocytes. Postinflammatory foci of lung fibrosis were evident after 1–2 months. The fibrotic foci in lung stroma contained clusters of GFP+ CD45+ cells, GFP+ vimentin-positive cells, and GFP+ collagen I-positive fibroblasts. GFP+ endothelial or epithelial cells were not identified. These data suggest that following 5-Gy irradiation and acute bacterial pneumonia, BMDC may temporarily participate in lung postinflammatory repair and stromal remodeling without long-term engraftment as specialized endothelial or epithelial cells.
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Martin C, Papazian L, Payan MJ, Saux P, Gouin F (1995) Pulmonary fibrosis correlates with outcome in adult respiratory distress syndrome. A study in mechanically ventilated patients. Chest 107:196–200
Molina-Molina M, Badia JR, Marin-Arguedas A, Xaubet A, Santos MJ, Nicolas JM, Ferrer M, Torres A (2003) Outcomes and clinical characteristics of patients with pulmonary fibrosis and respiratory failure admitted to an intensive care unit. A study of 20 cases. Med Clin (Barc) 121:63–67
Chapman HA (2004) Disorders of lung matrix remodeling. J Clin Invest 113:148–157
Gross TJ, Hunninghake GW (2001) Idiopathic pulmonary fibrosis. N Engl J Med 345:517–525
Antoniou KM, Bouros D, Siafakas NM (2004) Top ten list in idiopathic pulmonary fibrosis. Chest 125:1885–1887
Torry DJ, Richards CD, Podor TJ, Gauldie J (1994) Anchorage-independent colony growth of pulmonary fibroblasts derived from fibrotic human lung tissue. J Clin Invest 93:1525–1532
Theise ND, Henegariu O, Grove J, Jagirdar J, Kao PN, Crawford JM, Badve S, Saxena R, Krause DS (2002) Radiation pneumonitis in mice: a severe injury model for pneumocyte engraftment from bone marrow. Exp Hematol 30:1333–1338
Abe S, Boyer C, Liu X, Wen FQ, Kobayashi T, Fang Q, Wang X, Hashimoto M, Sharp JG, Rennard SI (2004) Cells derived from the circulation contribute to the repair of lung injury. Am J Respir Crit Care Med 170:1158–163
Ortiz L, Gambelli F, McBride C, Gaupp D, Baddoo M, Kaminski N, Phinney DG (2003) Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin exposure and ameliorates its fibrotic effects. Proc Natl Acad Sci U S A 100:8407–8411
Krause DS, Theise ND, Collector MI, Henegariu O, Hwang S, Gardner R, Neutzel S, Sharkis S (2001) Multi-organ, multi-lineage engraftment by a single bone marrow-derived stem cell. Cell 105:369–377
Wagers A, Sherwood R, Christensen J, Weissman IL (2002) Little evidence for developmental plasticity of adult hematopoietic stem cell. Science 297:2256–2259
Grove J, Lutzko C, Priller J, Henegariu O, Theise ND, Kohn D, Krause DS (2002) Marrow-derived cells as vehicles for delivery of gene therapy to pulmonary epithelium. Am J Respir Cell Mol Biol 27:645–651
Abe S, Laube G, Boyer C, Rennard SI, Sharp JG (2003) Transplanted BM and BM side population cells contribute progeny to the lung and liver in irradiated animals. Cytotherapy 5:523–533
Kotton DN, Ma BY, Cardoso WV, Sanderson EA, Summer RS, Williams MC, Fine A (2001) Bone-marrow-derived cells as progenitors of lung alveolar epithelium. Development 128:5181–5188
Yamada M, Kubo H, Kobayashi S, Ishizawa K, Numasaki M, Ueda S, Suzuki T, Sasaki H (2004) Bone-marrow-derived progenitor cells are important for lung repair after lipopolysaccharide-induced lung injury. J Immunol 172:1266–1272
Suratt B, Cool C, Serls A, Chen L, Varella-Garcia M, Shpall E, Brown K, Worthen GS (2003) Human pulmonary chimerisms after hematopoietic stem cell transplantation. Am J Respir Crit Care Med 168:318–322
Kleeberger W, Versmold A, Rothhamel T, Glockner S, Bredt M, Haverich A, Lehmann U, Kreipe H (2003) Increased chimerism of bronchial and alveolar epithelium in human lung allografts undergoing chronic injury. Am J Pathol 162:1487–1494
Zander DS, Baz MA, Cogle CR, Visner GA, Thiese ND, Crawford JM (2005) Bone marrow-derived stem cell repopulation contributes minimally to the type II pneumocyte pool in transplanted human lungs. Transplantation 80:206–212
Zander DS, Cogle CR, Thiese ND, Crawford JM (2006) Donor-derived type II pneumocytes are rare in the lungs of allogeneic hematopoietic cell transplant recipients. Ann Clin Lab Sci 36:47–52
Weiss DJ, Berberich MA, Borok Z, Gail DB, Kolls JK, Penland C, Prockop D (2006) Adult stem sells, lung biology and lung disease. Proc Am Thorac Soc 3:193–207
Van Haaften T, Thebald B (2006) Adult bone marrow-derived stem cells for the lung: implications for pediatric lung diseases. Pediatr Res 59(4):94R–99R
Gupta N, Su X, Popov B, Lee JW, Serikov V, Matthay MA (2007) Intrapulmonary delivery of bone marrow-derived mesenchymal stem cells improves survival and attenuates endotoxin-induced acute lung injury in mice. J Immunol 179:1855–1863
Serikov VB, Popov B, Mikhaylov VM, Gupta N, Matthay MA (2007) Evidence of temporary airway epithelial repopulation and rare clonal formation by BM-derived cells following naphthalene injury in mice. Anat Rec 290:1033–1046
Popov B, Serikov VB, Petrov NS, Izusova TV, Gupta N, Matthay MA (2007) Lung epithelial cells A549 induce endodermal differentiation in mouse mesenchymal BM stem cells by a paracrine mechanism. Tissue Eng 13:2441–2450
Liang Y, VanZant G, Szilvassy SJ (2005) Effects of aging on the homing and engraftment of murine hematopoietic stem and progenitor cells. Blood 106:1479–1487
Morrison SJ, Wandycz AM, Akashi K, Globerson A, Weissman IL (1996) The aging of hematopoietic stem cells. Nat Med 2:1011–1016
Kim M, Moon H, Spangrude GJ (2003) Major age-related changes of mouse hematopoietic stem/progenitor cells. Ann N Y Acad Sci 996:195–208
Zander DS, Cogle CR, Theise ND, Crawford JM (2206) Donor-derived type II pneumocytes are rare in the lungs of allogeneic hematopoietic cell transplant recipients. Ann Clin Lab Sci 36:47–52
Reynolds SD, Giangreco A, Hong KU, McGrath KE, Ortiz LA, Stripp BR (2004) Airway injury in lung disease pathophysiology: selective depletion of airway stem and progenitor cell pools potentiates lung inflammation and alveolar dysfunction. Am J Physiol Lung Cell Mol Physiol 287:L1256-L1265
Schmidt M, Sun G, Stacey MA, Mori L, Mattoli S (2003) Identification of circulating fibroblasts as precursors of bronchial myofibroblasts in asthma. J Immunol 170:380–389
London L, Majeski E, Paintlia MK, Harley RA, London SD (2002) Respiratory reovirus 1/L induction of diffuse alveolar damage: A model of Acute Respiratory Distress Syndrome. Exp Mol Pathol 72:24–36
Majeski EI, Harley RA, Bellum SC, London SD, London L (2003) Differential role for T cells in development of fibrotic leasions associated with reovirus 1/L-induced bronchiolitis obliterans organizing pneumonia versus acute respiratory distress syndrome. Am J Respir Cell Mol Biol 28:208–217
Hashimoto N, Jin H, Liu T, Chensue SW, Phan SH (2004) Bone-marrow-derived progenitor cells in pulmonary fibrosis. JCI 113:243–252
Prockop DJ (1997) Marrow stromal cells as stem cells for nonhematopoietic tissues. Science 276:71–74
Prockop DJ, Gregory CA, Spees JL (2003) One strategy for cell and gene therapy: harnessing the power of adult stem cells to repair tissues. Proc Natl Acad Sci U S A 100:11917–11923
Pitt BR, Ortiz LA (2004) Stem cells in lung biology. Am J Physiol Lung Cell Mol Physiol 286:L621–L622
Acknowledgments
Antibodies were a gift from Dr. J. H. Widdicombe (UC Davis). V. Mikhaylov supported by RFBR 06-0406388 OFI.
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Serikov, V.B., Mikhaylov, V.M., Krasnodembskay, A.D. et al. Bone Marrow-Derived Cells Participate in Stromal Remodeling of the Lung Following Acute Bacterial Pneumonia in Mice. Lung 186, 179–190 (2008). https://doi.org/10.1007/s00408-008-9078-6
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DOI: https://doi.org/10.1007/s00408-008-9078-6