251. Involvement of granulocyte-macrophage colony-stimulating factor in pulmonary homeostasis.
- Author
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Dranoff G, Crawford AD, Sadelain M, Ream B, Rashid A, Bronson RT, Dickersin GR, Bachurski CJ, Mark EL, and Whitsett JA
- Subjects
- Animals, Bronchoalveolar Lavage Fluid chemistry, Granulocyte-Macrophage Colony-Stimulating Factor genetics, Hematopoiesis, Homeostasis, Humans, Hyperplasia, Mice, Mice, Inbred C57BL, Mutation, Proteolipids metabolism, Pulmonary Alveolar Proteinosis metabolism, Pulmonary Alveoli pathology, Pulmonary Surfactant-Associated Proteins, Granulocyte-Macrophage Colony-Stimulating Factor physiology, Lung pathology, Pulmonary Alveolar Proteinosis pathology, Pulmonary Alveoli metabolism, Pulmonary Surfactants metabolism
- 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.
- Published
- 1994
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