Granulocyte-macrophage colony-stimulating factor increases surfactant phospholipid in premature rabbits.
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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Department of Pediatrics, University of California Irvine, Orange 92668, USA.
Bry
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Lappalainen
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Hallman
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D000818:Animals; D002452:Cell Count / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005865:Gestational Age; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D010713:Phosphatidylcholines / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D011510:Proteolipids / Q000096:biosynthesis; D011663:Pulmonary Surfactants / Q000096:biosynthesis / Q000378:metabolism*; D011817:Rabbits; D011994:Recombinant Proteins
D010713:Phosphatidylcholines; D010743:Phospholipids; D011510:Proteolipids; D011663:Pulmonary Surfactants; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor