Y. Shibata et al., GM-CSF regulates alveolar macrophage differentiation and innate immunity in the lung through PU.1, IMMUNITY, 15(4), 2001, pp. 557-567
GM-CSF gene targeted (GM(-/-)) mice are susceptible to respiratory infectio
ns and develop alveolar proteinosis due to defects in innate immune functio
n and surfactant catabolism in alveolar macrophages (AMs), respectively. Re
duced cell adhesion, phagocytosis, pathogen killing, mannose- and Toll-like
receptor expression, and LPS- or peptidoglycan-stimulated TNF alpha, relea
se were observed in AMs from GM(-/-) mice. The transcription factor PU.1 wa
s markedly reduced in AMs of GM(-/-) mice in vivo and was restored by selec
tive expression of GM-CSF in the lungs of SPC-GM/GM(-/-) transgenic mice. R
etrovirus-mediated expression of PU.1 in AMs from GM(-/-) mice rescued host
defense functions and surfactant catabolism by AMs. We conclude that PU.1
mediates GM-CSF-dependent effects on terminal differentiation of AMs regula
ting innate immune functions and surfactant catabolism by AMs.