The biological consequences of excess GM-CSF levels in transgenic mice also lacking high-affinity receptors for GM-CSF
- Author(s)
- Metcalf, D; Mifsud, S; Di Rago, L; Robb, L; Nicola, NA; Alexander, W;
- Details
- Publication Year 1998-03,Volume 12,Issue #3,Page 353-362
- Journal Title
- LEUKEMIA
- Publication Type
- Journal Article
- Abstract
- GM-CSF transgenic mice were crossed with mice with homozygous inactivation of the gene encoding the common beta chain (beta c) of the CM-CSF receptor to produce mice with constitutively elevated GM-CSF levels but no high-affinity GM-CSF receptors. GM-CSF transgenic beta -/- mice had exceptionally elevated serum GM-CSF levels but failed to develop the abnormal peritoneal cell population, eye destruction or tissue lesions characteristic of GM-CSF transgenic beta c +/+ mice. The alveolar proteinosis of beta c -/- mice was not altered in GM-CSF transgenic beta c -/- mice. Levels of GM-CSF mRNA in transgenic GMCSF beta c -/- were elevated but lower than in transgenic beta +/+ mice and the higher serum GM-CSF levels were traced in part to the longer serum half-life of GM-CSF in beta c -/- than in beta c +/+ mice although urinary loss of GM-CSF was higher in beta c -/- than in +/+ mice. The data indicate that the transgenic phenotype was due to stimulation by GM-CSF and not an insertional effect, that low-affinity receptors are not capable of initiating tissue pathology even in the presence of excess GM-CSF levels and that autocrine production of GM-CSF by GM-CSF-responsive cells also fails to induce changes in these cells. The results support current dogma that the action of polypeptide regulators is mediated exclusively by activation of high-affinity membrane receptors.
- Publisher
- STOCKTON PRESS
- Keywords
- COLONY-STIMULATING FACTOR; GROWTH-FACTOR; HEMATOPOIETIC-CELLS; DEFICIENT MICE; EXPRESSION; TRANSFORMATION; PROLIFERATION; INTERLEUKIN-3; MACROPHAGES; PERITONEAL
- Publisher's Version
- https://doi.org/10.1038/sj.leu.2400926
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 1998-03-01 12:00:00