4.4 Article

Mobilization of Bone Marrow Cells by CSF3 Protects Mice from Bleomycin-Induced Lung Injury

Journal

RESPIRATION
Volume 82, Issue 4, Pages 358-368

Publisher

KARGER
DOI: 10.1159/000328762

Keywords

Lung fibrosis; Bleomycin; Bone marrow stem cells; CSF3

Funding

  1. National Science Foundation of China [30671996, 30971323]
  2. Science and Technology Commission of Shanghai Municipality [044119637, 044107050, 064107050, 08411961000, 0852nm05600, 09411951500]
  3. Shanghai Subject Chief Scientist [08XD14034]
  4. National 973 [2010CB945600, 2010CB945601]

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Background: Bone marrow-derived cells may play a role in tissue injury and repair. Growth factors facilitate the mobilization of bone marrow-derived cells to the site of injury. Objectives: The aim of this study was to determine the effect of the mobilization of autologous bone marrow-derived cells by granulocyte colony-stimulating factor (CSF3) on bleomycin-induced lung injury in mice. Methods: The bone marrow from male green fluorescent protein transgenic (C57Bl/6J) mice was transplanted into irradiated female C57Bl/6J mice. Bleomycin lung injury was induced in these bone marrow-reconstituted mice and unreconstituted C57Bl/6J mice, and some mice were treated with recombinant CSF3. Lung histology, survival, cytokine expression and matrix metalloproteinase (MMP) expression were evaluated to determine the effect of CSF3 after bleomycin-induced lung injury. Results: Histology and flow cytometry analysis showed successful mobilization of bone marrow-derived cells by CSF3 treatment in the recipient lungs. Importantly, CSF3 attenuated bleomycin-induced lung injury and improved survival. Furthermore, CSF3 administration regulated transforming growth factor-beta, interferon-gamma, MMP9 and tissue inhibitors of MMP1 expression during bleomycin injury. Conclusions: These data demonstrated that the mobilization of bone marrow-derived cells by CSF3 has a protective effect against bleomycin-induced lung injury and fibrosis. Copyright (C) 2011 S. Karger AG, Basel

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