Transfer of granulocyte-macrophage colony-stimulating factor gene to rat lung induces eosinophilia, monocytosis, and fibrotic reactions

J Clin Invest. 1996 Feb 15;97(4):1102-10. doi: 10.1172/JCI118503.

Abstract

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pleiotropic cytokine whose expression is increased in numerous respiratory diseases, particularly in asthma. However, the role of GM-CSF in the pathogenesis of these conditions in vivo remains unclear. Here, we report the functional activities of GM-CSF highly expressed in rat lung after intrapulmonary transfer of the gene coding for murine GM-CSF by using an adenoviral vector. This high, transient expression of GM-CSF led to the sustained but self-limiting accumulation of eosinophils and macrophages associated with tissue injury in the lung followed by varying degrees of irreversible fibrotic reactions observed in later stages. These results suggest that GM-CSF plays a previously unrealized role in the development of respiratory conditions characterized by eosinophilia, granuloma and/or fibrosis and provide the rationale for targeting this molecule in these diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Bronchoalveolar Lavage Fluid / cytology
  • DNA Primers / chemistry
  • Eosinophilia / etiology*
  • Eosinophilia / pathology
  • Gene Transfer Techniques
  • Genetic Vectors
  • Granulocyte-Macrophage Colony-Stimulating Factor / physiology*
  • Granuloma
  • Leukocyte Count
  • Lung / pathology
  • Macrophages
  • Male
  • Molecular Sequence Data
  • Pulmonary Fibrosis / etiology*
  • Pulmonary Fibrosis / pathology
  • Rats

Substances

  • DNA Primers
  • Granulocyte-Macrophage Colony-Stimulating Factor