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Science 29 April 1994:
Vol. 264. no. 5159, pp. 713 - 716
DOI: 10.1126/science.8171324
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Articles

Science, Vol 264, Issue 5159, 713-716
Copyright © 1994 by American Association for the Advancement of Science

articles

Involvement of granulocyte-macrophage colony-stimulating factor in pulmonary homeostasis

G Dranoff, AD Crawford, M Sadelain, B Ream, A Rashid, RT Bronson, GR Dickersin, CJ Bachurski, EL Mark, JA Whitsett, and al. et

Whitehead Institute for Biomedical Research, Cambridge, MA.

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.


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M. deFelice, D. Silberschmidt, R. DiLauro, Y. Xu, S. E. Wert, T. E. Weaver, C. J. Bachurski, J. C. Clark, and J. A. Whitsett (2003)
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G. PLENZ, H. ESCHERT, S. BEISSERT, V. ARPS, J. R. SINDERMANN, H. ROBENEK, and W. VOLKER (2003)
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S. Chabot, K. Koumanov, G. Lambeau, M. H. Gelb, V. Balloy, M. Chignard, J. A. Whitsett, and L. Touqui (2003)
J. Immunol. 171, 995-1000
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S. Weng, L. Zemany, K. N. Standley, D. V. Novack, M. La Regina, C. Bernal-Mizrachi, T. Coleman, and C. F. Semenkovich (2003)
PNAS 100, 6730-6735
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Deficiencies of GM-CSF and Interferon {gamma} Link Inflammation and Cancer.
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   Abstract »    Full Text »    PDF »
Endocytic Internalization of Adenovirus, Nonspecific Phagocytosis, and Cytoskeletal Organization Are Coordinately Regulated in Alveolar Macrophages by GM-CSF and PU.1.
P.-Y. Berclaz, Z. Zsengeller, Y. Shibata, K. Otake, S. Strasbaugh, J. A. Whitsett, and B. C. Trapnell (2002)
J. Immunol. 169, 6332-6342
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GM-CSF, via PU.1, regulates alveolar macrophage Fcgamma R-mediated phagocytosis and the IL-18/IFN-gamma -mediated molecular connection between innate and adaptive immunity in the lung.
P.-Y. Berclaz, Y. Shibata, J. A. Whitsett, and B. C. Trapnell (2002)
Blood 100, 4193-4200
   Abstract »    Full Text »    PDF »
Autoantibodies against Granulocyte Macrophage Colony-Stimulating Factor Are Diagnostic for Pulmonary Alveolar Proteinosis.
T. L. Bonfield, D. Russell, S. Burgess, A. Malur, M. S. Kavuru, and M. J. Thomassen (2002)
Am. J. Respir. Cell Mol. Biol. 27, 481-486
   Abstract »    Full Text »    PDF »
Pulmonary Alveolar Proteinosis: Treatment by Bronchofiberscopic Lobar Lavage.
S.-L. Cheng, H.-T. Chang, H.-P. Lau, L.-N. Lee, and P.-C. Yang (2002)
Chest 122, 1480-1485
   Abstract »    Full Text »    PDF »
Normal Remodeling of the Oxygen-Injured Lung Requires the Cyclin-Dependent Kinase Inhibitor p21Cip1/WAF1/Sdi1.
R. J. Staversky, R. H. Watkins, T. W. Wright, E. Hernady, M. B. LoMonaco, C. T. D'Angio, J. P. Williams, W. M. Maniscalco, and M. A. O'Reilly (2002)
Am. J. Pathol. 161, 1383-1393
   Abstract »    Full Text »    PDF »
Surfactant Protein D Reduces Alveolar Macrophage Apoptosis In Vivo.
H. Clark, N. Palaniyar, P. Strong, J. Edmondson, S. Hawgood, and K. B. M. Reid (2002)
J. Immunol. 169, 2892-2899
   Abstract »    Full Text »    PDF »
Pulmonary Alveolar Proteinosis: Progress in the First 44 Years.
J. F. Seymour and J. J. Presneill (2002)
Am. J. Respir. Crit. Care Med. 166, 215-235
   Abstract »    Full Text »    PDF »
Role of the respiratory burst in co-operative reduction in neutrophil survival by influenza A virus and Escherichia coli.
G. ENGELICH, M. WHITE, and K. L. HARTSHORN (2002)
J. Med. Microbiol. 51, 484-490
   Abstract »    Full Text »    PDF »
Immunolocalization of Surfactant Protein-D (SP-D) in Human Fetal, Newborn, and Adult Tissues.
M. T. Stahlman, M. E. Gray, W. M. Hull, and J. A. Whitsett (2002)
J. Histochem. Cytochem. 50, 651-660
   Abstract »    Full Text »    PDF »
Spontaneous generation and survival of blood dendritic cells in mononuclear cell culture without exogenous cytokines.
C. S. K. Ho, D. Munster, C. M. Pyke, D. N. J. Hart, and J. A. Lopez (2002)
Blood 99, 2897-2904
   Abstract »    Full Text »    PDF »
Erythropoietin receptor haploinsufficiency and in vivo interplay with granulocyte-macrophage colony-stimulating factor and interleukin 3.
A. G. Jegalian, A. Acurio, G. Dranoff, and H. Wu (2002)
Blood 99, 2603-2605
   Abstract »    Full Text »    PDF »
BAL findings in a patient with pulmonary alveolar proteinosis successfully treated with GM-CSF.
O D Schoch, U Schanz, M Koller, K Nakata, J F Seymour, E W Russi, and A Boehler (2002)
Thorax 57, 277-280
   Abstract »    Full Text »    PDF »
Impaired functional activity of alveolar macrophages from GM-CSF-deficient mice.
R. Paine III, S. B. Morris, H. Jin, S. E. Wilcoxen, S. M. Phare, B. B. Moore, M. J. Coffey, and G. B. Toews (2001)
Am J Physiol Lung Cell Mol Physiol 281, L1210-L1218
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Alveolar macrophage deficiency in osteopetrotic mice deficient in macrophage colony-stimulating factor is spontaneously corrected with age and associated with matrix metalloproteinase expression and emphysema.
Y. Shibata, Z. Zsengeller, K. Otake, N. Palaniyar, and B. C. Trapnell (2001)
Blood 98, 2845-2852
   Abstract »    Full Text »    PDF »
SP-D and GM-CSF regulate surfactant homeostasis via distinct mechanisms.
M. Ikegami, W. M. Hull, M. Yoshida, S. E. Wert, and J. A. Whitsett (2001)
Am J Physiol Lung Cell Mol Physiol 281, L697-L703
   Abstract »    Full Text »    PDF »
Pulmonary alveolar proteinosis: a complete response to GM-CSF therapy.
R M Barraclough and A J Gillies (2001)
Thorax 56, 664-665
   Abstract »    Full Text »    PDF »
GM-CSF mediates alveolar macrophage proliferation and type II cell hypertrophy in SP-D gene-targeted mice.
S. Hawgood, J. Akiyama, C. Brown, L. Allen, G. Li, and F. R. Poulain (2001)
Am J Physiol Lung Cell Mol Physiol 280, L1148-L1156
   Abstract »    Full Text »    PDF »
Basis of hematopoietic defects in platelet-derived growth factor (PDGF)-B and PDGF {beta}-receptor null mice.
W. E. Kaminski, P. Lindahl, N. L. Lin, V. C. Broudy, J. R. Crosby, M. Hellstrom, B. Swolin, D. F. Bowen-Pope, P. J. Martin, R. Ross, et al. (2001)
Blood 97, 1990-1998
   Abstract »    Full Text »    PDF »


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