Aerosolized GM-CSF ameliorates pulmonary alveolar proteinosis in GM-CSF-deficient mice

Am J Physiol. 1999 Apr;276(4):L556-63. doi: 10.1152/ajplung.1999.276.4.L556.


Surfactant proteins and phospholipids accumulate in the alveolar spaces and lung tissues of mice deficient in granulocyte-macrophage colony-stimulating factor (GM-CSF), with pathological findings resembling the histology seen in the human disease pulmonary alveolar proteinosis (PAP). Previous metabolic studies in GM-CSF-deficient [GM(-/-)] mice indicated that defects in surfactant clearance cause the surfactant accumulation in PAP. In the present study, GM(-/-) mice were treated daily or weekly with recombinant mouse GM-CSF by aerosol inhalation or intraperitoneal injection for 4-5 wk. Lung histology, alveolar macrophage differentiation, and surfactant protein B immunostaining returned toward normal levels in the GM-CSF aerosol-treated mice. Alveolar and lung tissue saturated phosphatidylcholine and surfactant protein B concentrations were significantly decreased after treatment with aerosolized GM-CSF. Cessation of aerosolized GM-CSF for 5 wk resulted in increased saturated phosphatidylcholine pool sizes that returned to pretreatment levels. In contrast, PAP did not improve in GM(-/-) mice treated daily for 5 wk with larger doses of systemic GM-CSF. Aerosolized GM-CSF improved PAP in the GM(-/-) mice, demonstrating that surfactant homeostasis can be influenced by local administration of GM-CSF to the respiratory tract.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Inhalation
  • Aerosols
  • Animals
  • Drug Administration Schedule
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / deficiency*
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology*
  • Humans
  • Lung / drug effects
  • Lung / pathology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Pulmonary Alveolar Proteinosis / genetics*
  • Pulmonary Alveolar Proteinosis / pathology
  • Pulmonary Alveolar Proteinosis / therapy*
  • Pulmonary Alveoli / drug effects
  • Pulmonary Alveoli / pathology


  • Aerosols
  • Granulocyte-Macrophage Colony-Stimulating Factor