GM-CSF regulates protein and lipid catabolism by alveolar macrophages.
Metabolism of surfactant protein (SP) A and dipalmitoylphosphatidylcholine (DPPC) was assessed in alveolar macrophages isolated from granulocyte-macrophage colony-stimulated factor (GM-CSF) gene-targeted [GM(-/-)] mice, wild-type mice, and GM(-/-) mice expressing GM-CSF under control of the SP-C promoter element (SP-C-GM). Although binding and uptake of (125)I-SP-A were significantly increased in alveolar macrophages from GM(-/-) compared with wild type or SP-C-GM mice, catabolism of (125)I-SP-A was markedly decreased in GM(-/-) mice. Association of [(3)H]DPPC with alveolar macrophages from GM(-/-), wild-type, and SP-C-GM mice was similar; however, catabolism of DPPC was markedly reduced in cells from GM(-/-) mice. Fluorescence-activated cell sorter analysis demonstrated decreased catabolism of rhodamine-labeled dipalmitoylphosphatidylethanolamine by alveolar macrophages from GM(-/-) mice. GM-CSF deficiency was associated with increased SP-A uptake by alveolar macrophages but with impaired surfactant lipid and SP-A degradation. These findings demonstrate the important role of GM-CSF in the regulation of alveolar macrophage lipid and SP-A catabolism.
Yoshida
M
M
Division of Pulmonary Biology, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA.
Ikegami
M
M
Reed
J A
JA
Chroneos
Z C
ZC
Whitsett
J A
JA
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000378:metabolism; D000818:Animals; D005456:Fluorescent Dyes; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000502:physiology*; D006801:Humans; D050356:Lipid Metabolism; D016676:Macrophages, Alveolar / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D011506:Proteins / Q000378:metabolism*; D011510:Proteolipids / Q000378:metabolism; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000378:metabolism; D012235:Rhodamines
D005456:Fluorescent Dyes; D011506:Proteins; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D012235:Rhodamines; D015060:1,2-Dipalmitoylphosphatidylcholine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor