Transfer of granulocyte-macrophage colony-stimulating factor gene to rat lung induces eosinophilia, monocytosis, and fibrotic reactions.
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.
Xing
Z
Z
Department of Pathology, Health Sciences Center, McMaster University, Hamilton, Ontario, L8N3Z5, Canada.
Ohkawara
Y
Y
Jordana
M
M
Graham
F
F
Gauldie
J
J
D000818:Animals; D001483:Base Sequence; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D017931:DNA Primers / Q000737:chemistry; D004802:Eosinophilia / Q000209:etiology* / Q000473:pathology; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000502:physiology*; D006099:Granuloma; D007958:Leukocyte Count; D008168:Lung / Q000473:pathology; D008264:Macrophages; D008297:Male; D008969:Molecular Sequence Data; D011658:Pulmonary Fibrosis / Q000209:etiology* / Q000473:pathology; D051381:Rats
D017931:DNA Primers; D016178:Granulocyte-Macrophage Colony-Stimulating Factor