ALUNG Apr. 20/4

Reed, Jacquelyn A., Machiko Ikegami, Eli R. Cianciolo, Wei Lu, Patricia S. Cho, William Hull, Alan H. Jobe, and JeffreyA. Whitsett. Aerosolized GM-CSF ameliorates pulmonary alveolar proteinosis in GM-CSF-deficient mice. Am. J. Physiol. 276 (Lung Cell. Mol. Physiol. 20): L556–L563, 1999.—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-CSFdeficient [GM(2/2)] mice indicated that defects in surfactant clearance cause the surfactant accumulation in PAP. In the present study, GM(2/2) 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(2/2) mice treated daily for 5 wk with larger doses of systemic GM-CSF. Aerosolized GM-CSF improved PAP in the GM(2/2) mice, demonstrating that surfactant homeostasis can be influenced by local administration of GM-CSF to the respiratory tract.