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

• Published in: The American journal of physiology Vol. 273; no. 4; p. L715
• Main Authors: Huffman Reed, J A, Rice, W R, Zsengellér, Z K, Wert, S E, Dranoff, G, Whitsett, J A
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01-10-1997
• Subjects: Animals; Body Weight; Bronchoalveolar Lavage Fluid - chemistry; Enzyme-Linked Immunosorbent Assay; Epithelial Cells - metabolism; Epithelial Cells - pathology; Granulocyte-Macrophage Colony-Stimulating Factor - biosynthesis; Granulocyte-Macrophage Colony-Stimulating Factor - genetics; Granulocyte-Macrophage Colony-Stimulating Factor - physiology; Humans; Hyperplasia; Lipopolysaccharides - toxicity; Lung - growth & development; Lung - pathology; Lung - physiology; Mice; Mice, Knockout; Mice, Transgenic; Organ Size; Proteolipids - biosynthesis; Proteolipids - physiology; Pulmonary Alveoli - metabolism; Pulmonary Alveoli - pathology; Pulmonary Surfactants - biosynthesis; Pulmonary Surfactants - physiology; Recombinant Fusion Proteins - biosynthesis; Salmonella typhimurium
• ISSN: 0002-9513; 2163-5773
• DOI: 10.1152/ajplung.1997.273.4.l715

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.