title: Aerosolized GM-CSF ameliorates pulmonary alveolar proteinosis in GM-CSF-deficient mice.
abstract: 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.
authors: Division of Pulmonary Biology, Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
authors: J A
authors: JA
authors: Reed
authors: M
authors: M
authors: Ikegami
authors: E R
authors: ER
authors: Cianciolo
authors: W
authors: W
authors: Lu
authors: P S
authors: PS
authors: Cho
authors: W
authors: W
authors: Hull
authors: A H
authors: AH
authors: Jobe
authors: J A
authors: JA
authors: Whitsett
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D004334:Drug Administration Schedule; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000172:deficiency* / Q000235:genetics / Q000494:pharmacology*; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011649:Pulmonary Alveolar Proteinosis / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000473:pathology
chemical_list: D000336:Aerosols; D016178:Granulocyte-Macrophage Colony-Stimulating Factor