title: Involvement of granulocyte-macrophage colony-stimulating factor in pulmonary homeostasis.
abstract: The in vivo function of murine granulocyte-macrophage colony-stimulating factor (GM-CSF) was investigated in mice, carrying a null allele of the GM-CSF gene, that were generated by gene targeting techniques in embryonic stem cells. Although steady-state hematopoiesis was unimpaired in homozygous mutant animals, all animals developed the progressive accumulation of surfactant lipids and proteins in the alveolar space, the defining characteristic of the idiopathic human disorder pulmonary alveolar proteinosis. Extensive lymphoid hyperplasia associated with lung airways and blood vessels was also found, yet no infectious agents could be detected. These results demonstrate that GM-CSF is not an essential growth factor for basal hematopoiesis and reveal an unexpected, critical role for GM-CSF in pulmonary homeostasis.
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA.
authors.forename: G
authors.initials: G
authors.lastname: Dranoff
authors.forename: A D
authors.initials: AD
authors.lastname: Crawford
authors.forename: M
authors.initials: M
authors.lastname: Sadelain
authors.forename: B
authors.initials: B
authors.lastname: Ream
authors.forename: A
authors.initials: A
authors.lastname: Rashid
authors.forename: R T
authors.initials: RT
authors.lastname: Bronson
authors.forename: G R
authors.initials: GR
authors.lastname: Dickersin
authors.forename: C J
authors.initials: CJ
authors.lastname: Bachurski
authors.forename: E L
authors.initials: EL
authors.lastname: Mark
authors.forename: J A
authors.initials: JA
authors.lastname: Whitsett
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000502:physiology*; D006410:Hematopoiesis; D006706:Homeostasis; D006801:Humans; D006965:Hyperplasia; D008168:Lung / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D011510:Proteolipids / Q000378:metabolism; D011649:Pulmonary Alveolar Proteinosis / Q000378:metabolism / Q000473:pathology*; D011650:Pulmonary Alveoli / Q000378:metabolism* / Q000473:pathology; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000378:metabolism*
chemical_list: D011510:Proteolipids; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D016178:Granulocyte-Macrophage Colony-Stimulating Factor