TY - JOUR
T1 - GM-CSF regulates alveolar macrophage differentiation and innate immunity in the lung through PU.1
AU - Shibata, Yoko
AU - Berclaz, Pierre Yves
AU - Chroneos, Zissis C.
AU - Yoshida, Mitsuhiro
AU - Whitsett, Jeffrey A.
AU - Trapnell, Bruce C.
N1 - Funding Information:
We thank Dr. Harinder Singh for the gift of the PU.1/GFP- and GFP-expressing retroviral vectors; Dr. Gary Ross for providing purified human SP-A; Jo Rae Wright for the gift of the clinical specimen of group B Streptococcus ; Muhammad Fazili for help with alveolar macrophage collection; Susan Wert for help with photomicroscopy; and Marc Rothenberg for critical reading of the manuscript. Supported by the Cystic Fibrosis Foundation (B.C.T and J.A.W.), TCHRF (B.C.T.), ROI HL69549-01 (B.C.T.), NIH SCOR HL56387 (J.A.W.), and SFMBG (P.-Y.B.).
PY - 2001
Y1 - 2001
N2 - GM-CSF gene targeted (GM-/-) mice are susceptible to respiratory infections and develop alveolar proteinosis due to defects in innate immune function and surfactant catabolism in alveolar macrophages (AMs), respectively. Reduced cell adhesion, phagocytosis, pathogen killing, mannose- and Toll-like receptor expression, and LPS- or peptidoglycan-stimulated TNFα release were observed in AMs from GM-/- mice. The transcription factor PU.1 was markedly reduced in AMs of GM-/- mice in vivo and was restored by selective expression of GM-CSF in the lungs of SPC-GM/GM-/- transgenic mice. Retrovirus-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 regulating innate immune functions and surfactant catabolism by AMs.
AB - GM-CSF gene targeted (GM-/-) mice are susceptible to respiratory infections and develop alveolar proteinosis due to defects in innate immune function and surfactant catabolism in alveolar macrophages (AMs), respectively. Reduced cell adhesion, phagocytosis, pathogen killing, mannose- and Toll-like receptor expression, and LPS- or peptidoglycan-stimulated TNFα release were observed in AMs from GM-/- mice. The transcription factor PU.1 was markedly reduced in AMs of GM-/- mice in vivo and was restored by selective expression of GM-CSF in the lungs of SPC-GM/GM-/- transgenic mice. Retrovirus-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 regulating innate immune functions and surfactant catabolism by AMs.
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U2 - 10.1016/S1074-7613(01)00218-7
DO - 10.1016/S1074-7613(01)00218-7
M3 - Article
C2 - 11672538
AN - SCOPUS:0034748924
SN - 1074-7613
VL - 15
SP - 557
EP - 567
JO - Immunity
JF - Immunity
IS - 4
ER -
