AJP - Lung Cellular and Molecular Physiology, Vol 273, Issue 4 715-L725, Copyright © 1997 by American Physiological Society

ARTICLES

GM-CSF enhances lung growth and causes alveolar type II epithelial cell hyperplasia in transgenic mice

J. A. Huffman Reed, W. R. Rice, Z. K. Zsengeller, S. E. Wert, G. Dranoff and J. A. Whitsett
Division of Pulmonary Biology, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA.

The human surfactant protein (SP)-C gene promoter was used to direct expression of mouse granulocyte macrophage colony-stimulating factor (GM-CSF; SP-C-GM mice) in lung epithelial cells in GM-CSF-replete (GM+/+) or GM-CSF null mutant (GM-/-) mice. Lung weight and volume were significantly increased in SP-C-GM mice compared with GM+/+ or GM-/- control mice. Immunohistochemical staining demonstrated marked type II cell hyperplasia, and immunofluorescent labeling for proliferating cell nuclear antigen was increased in type II cells of SP-C-GM mice. Abundance of type II cells per mouse lung was increased three- to fourfold in SP-C-GM mice compared with GM+/+ and GM-/- mice. GM-CSF increased bromodeoxyuridine labeling of isolated type II cells in vitro. Type II cells, alveolar macrophages, and endothelial and bronchiolar epithelial cells were stained by antibodies to the GM-CSF receptor alpha-subunit in both GM+/+ mice and GM-CSF gene-targeted mice that are also homozygous for the SP-C-GM transgene. High levels of GM-CSF expression in type II cells of transgenic mice increased lung size and caused type II cell hyperplasia, demonstrating an unexpected role for the molecule in the regulation of type II cell proliferation and differentiation.

This article has been cited by other articles:

				D.-H. Kim, D. Sandoval, J. A. Reed, E. K. Matter, E. G. Tolod, S. C. Woods, and R. J. Seeley The role of GM-CSF in adipose tissue inflammation Am J Physiol Endocrinol Metab, November 1, 2008; 295(5): E1038 - E1046. [Abstract] [Full Text] [PDF]

				M. N. Ballinger, L. L. N. Hubbard, T. R. McMillan, G. B. Toews, M. Peters-Golden, R. Paine III, and B. B. Moore Paradoxical role of alveolar macrophage-derived granulocyte-macrophage colony-stimulating factor in pulmonary host defense post-bone marrow transplantation Am J Physiol Lung Cell Mol Physiol, July 1, 2008; 295(1): L114 - L122. [Abstract] [Full Text] [PDF]

				P. C. Joshi, L. Applewhite, P. O. Mitchell, K. Fernainy, J. Roman, D. C. Eaton, and D. M. Guidot GM-CSF receptor expression and signaling is decreased in lungs of ethanol-fed rats Am J Physiol Lung Cell Mol Physiol, December 1, 2006; 291(6): L1150 - L1158. [Abstract] [Full Text] [PDF]

				M. Ochs, L. Knudsen, L. Allen, A. Stumbaugh, S. Levitt, J. R. Nyengaard, and S. Hawgood GM-CSF mediates alveolar epithelial type II cell changes, but not emphysema-like pathology, in SP-D-deficient mice Am J Physiol Lung Cell Mol Physiol, December 1, 2004; 287(6): L1333 - L1341. [Abstract] [Full Text] [PDF]

				A. K. Bauer, A. M. Malkinson, and S. R. Kleeberger Susceptibility to neoplastic and non-neoplastic pulmonary diseases in mice: genetic similarities Am J Physiol Lung Cell Mol Physiol, October 1, 2004; 287(4): L685 - L703. [Abstract] [Full Text] [PDF]

				A. Pelaez, R. I. Bechara, P. C. Joshi, L. A. S. Brown, and D. M. Guidot Granulocyte/macrophage colony-stimulating factor treatment improves alveolar epithelial barrier function in alcoholic rat lung Am J Physiol Lung Cell Mol Physiol, January 1, 2004; 286(1): L106 - L111. [Abstract] [Full Text] [PDF]

				C. L. S. George, M. L. White, M. E. O'Neill, P. S. Thorne, D. A. Schwartz, and J. M. Snyder Altered surfactant protein A gene expression and protein metabolism associated with repeat exposure to inhaled endotoxin Am J Physiol Lung Cell Mol Physiol, December 1, 2003; 285(6): L1337 - L1344. [Abstract] [Full Text] [PDF]

				R. P. Charbeneau, P. J. Christensen, C. J. Chrisman, R. Paine III, G. B. Toews, M. Peters-Golden, and B. B. Moore Impaired synthesis of prostaglandin E2 by lung fibroblasts and alveolar epithelial cells from GM-CSF-/- mice: implications for fibroproliferation Am J Physiol Lung Cell Mol Physiol, June 1, 2003; 284(6): L1103 - L1111. [Abstract] [Full Text] [PDF]

				J. Burg, V. Krump-Konvalinkova, F. Bittinger, and C. J. Kirkpatrick GM-CSF expression by human lung microvascular endothelial cells: in vitro and in vivo findings Am J Physiol Lung Cell Mol Physiol, August 1, 2002; 283(2): L460 - L467. [Abstract] [Full Text] [PDF]

				B. B. Moore, M. J. Coffey, P. Christensen, S. Sitterding, R. Ngan, C. A. Wilke, R. McDonald, S. M. Phare, M. Peters-Golden, R. Paine III, et al. GM-CSF Regulates Bleomycin-Induced Pulmonary Fibrosis Via a Prostaglandin-Dependent Mechanism J. Immunol., October 1, 2000; 165(7): 4032 - 4039. [Abstract] [Full Text] [PDF]

				M. S. CARRAWAY, A. J. GHIO, J. D. CARTER, and C. A. PIANTADOSI Detection of Granulocyte-Macrophage Colony-Stimulating Factor in Patients with Pulmonary Alveolar Proteinosis Am. J. Respir. Crit. Care Med., April 1, 2000; 161(4): 1294 - 1299. [Abstract] [Full Text]