Mobilization of bone marrow cells by CSF3 protects mice from bleomycin-induced lung injury

Respiration. 2011;82(4):358-68. doi: 10.1159/000328762. Epub 2011 Jul 19.

Abstract

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-β, interferon-γ, 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic
  • Bleomycin
  • Bone Marrow Cells / drug effects*
  • Bone Marrow Cells / metabolism*
  • Female
  • Flow Cytometry
  • Gene Expression Regulation, Enzymologic
  • Granulocyte Colony-Stimulating Factor / pharmacology*
  • Green Fluorescent Proteins / genetics
  • Matrix Metalloproteinases / drug effects
  • Matrix Metalloproteinases / metabolism*
  • Mesenchymal Stem Cell Transplantation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Pulmonary Fibrosis / chemically induced
  • Pulmonary Fibrosis / pathology*
  • Pulmonary Fibrosis / prevention & control*
  • Recombinant Proteins / pharmacology

Substances

  • Antibiotics, Antineoplastic
  • Recombinant Proteins
  • Bleomycin
  • Granulocyte Colony-Stimulating Factor
  • Green Fluorescent Proteins
  • Matrix Metalloproteinases