Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mutation of the granulocyte-macrophage colony-stimulating factor (GM-CSF) gene by homologous recombination causes progressive pulmonary alveolar proteinosis (PAP) in GM-CSF-deficient mice (GM-/-). The present study tested whether adenovirus-mediated expression of GM-CSF alters the progression of PAP in GM-/- mice. Adult mice were pretreated with an anti-T cell receptor (TCR) antibody to block T cell-mediated immune response, followed by intratracheal instillation of deltaE1-E3 replication-deficient adenovirus expressing mouse GM-CSF (Av1mGM). Mice were killed 1, 3, and 5 weeks after treatment to assess lungs for GM-CSF, surfactant protein B (SP-B), alveolar macrophage maturation, and type II cell proliferation. GM-CSF was detected in BAL fluid from GM-/- mice 1 week after Av1mGM treatment, and GM-CSF mRNA was detected by RT-PCR through 5 weeks. Five weeks after Av1mGM treatment, PAP was improved and SP-B decreased as assessed by ELISA and immunostaining. Increased numbers of alveolar macrophages stained with alpha-naphthyl acetate esterase (alpha-NAE) following treatment with Av1mGM. Local expression of GM-CSF with a recombinant adenovirus ameliorated PAP in the GM-/- mice in association with enhanced maturation of alveolar macrophages.
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PMID:Adenovirus-mediated granulocyte-macrophage colony-stimulating factor improves lung pathology of pulmonary alveolar proteinosis in granulocyte-macrophage colony-stimulating factor-deficient mice. 975 36

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.
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PMID:Aerosolized GM-CSF ameliorates pulmonary alveolar proteinosis in GM-CSF-deficient mice. 1019 53

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a hematopoietic cytokine that is low in airway specimens from immature lungs at birth. In adult mice, an absence of GM-CSF causes excessive accumulation of alveolar surfactant due to a lack of catabolism. Our aim was to investigate whether recombinant human GM-CSF (rhGM-CSF) affects the pool sizes or the turnover of disaturated phosphatidylcholine (DPC) in preterm (gestation 29 d) rabbits at birth and in term rabbits, age 3 d. 3H-labeled dipalmitoyl phosphatidylcholine, 14C-acetate, and either rhGM-CSF (125 or 25 microg/kg body weight) or placebo were given intratracheally. Thereafter, the intra- and extracellular surfactant fractions were isolated and quantified for DPC and radioactivity. In preterm animals, GM-CSF increased dose-dependently within 24 h both the pool sizes of surfactant DPC and the 3H,14C-labeling of surfactant DPC (p < 0.05). The expression of surfactant protein B mRNA was unaffected, whereas surfactant protein B in bronchoalveolar lavage increased. The number of cells in the whole lung, the type II alveolar epithelial cells, and the lavageable alveolar macrophages were unaffected. At term, rhGM-CSF increased the turnover but did not affect the pool sizes of surfactant DPC. Intraperitoneal rhGM-CSF increased blood eosinophils but had no effect on surfactant DPC. Depending on the degree of lung maturity, GM-CSF in the alveolar space may either up-regulate the pool size or increase the turnover of surfactant phospholipid after birth.
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PMID:Granulocyte-macrophage colony-stimulating factor increases surfactant phospholipid in premature rabbits. 1054 27