INVOLVEMENT OF GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR IN PULMONARY HOMEOSTASIS

The in vivo function of murine granulocyte-macrophage colony-stimulati ng 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 unimpair ed 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 pulmonar y alveolar proteinosis. Extensive lymphoid hyperplasia associated with lung airways and blood vessels was also found, yet no infectious agen ts could be detected. These results demonstrate that GM-CSF is not an essential growth factor for basal hematopoiesis and reveal an unexpect ed, critical role for GM-CSF in pulmonary homeostasis.