Abstract
AbstractMice with a null mutation of the βc chain of the granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and IL-5 receptors (βc-null mice) develop an alveolar proteinosis-like lung disease. The pathogenesis of this disease is uncertain and, although a defect in alveolar macrophage function has been postulated, no previous analysis of mature hematopoietic cells in mice with alveolar proteinosis has been reported. Therefore, we undertook a functional analysis of the mature hematopoietic cell compartment in βc-null mice. In addition, we reexamined the roles of the GM-CSF receptor chain and the βc chain in signaling by GM-CSF. Neutrophils and macrophages from βc-null mice were capable of normal survival and phagocytosis in the absence of stimulus and of similar levels of nitric oxide production in response to interferon-γ and lipopolysaccharide. GM-CSF–mediated augmentation of survival, phagocytosis, and hydrogen-ion production were absent in neutrophils from βc-null mice. Interestingly, we were unable to show any ability of the GM-CSF receptor -chain alone to mediate glucose transport in these cells. In keeping with the βc-null mice lung pathology, examination of lavage fluid from the lungs of βc-null mice showed increased cellularity. This was caused by an increase in the number of lymphocytes, neutrophils, and macrophages. Large foamy cells in the lavage fluid from βc-null mice were identified as macrophages using immunohistochemistry. Functional analysis showed that these βc-null alveolar macrophages were capable of phagocytosis but uptake of colloidal carbon and cellular adhesion were reduced. In summary, mature hematopoietic cells with a null mutation of the βc receptor were unable to perform GM-CSF–mediated hematopoietic cell functions including glucose transport, but responded normally to a range of other ligands.
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Dates
Type | When |
---|---|
Created | 5 years, 10 months ago (Oct. 14, 2019, 6:19 a.m.) |
Deposited | 1 year, 11 months ago (Sept. 21, 2023, 12:48 p.m.) |
Indexed | 5 months, 1 week ago (March 29, 2025, 6:30 p.m.) |
Issued | 26 years, 9 months ago (Dec. 1, 1998) |
Published | 26 years, 9 months ago (Dec. 1, 1998) |
Published Print | 26 years, 9 months ago (Dec. 1, 1998) |
@article{Scott_1998, title={Functional Analysis of Mature Hematopoietic Cells From Mice Lacking the βc Chain of the Granulocyte-Macrophage Colony-Stimulating Factor Receptor}, volume={92}, ISSN={0006-4971}, url={http://dx.doi.org/10.1182/blood.v92.11.4119}, DOI={10.1182/blood.v92.11.4119}, number={11}, journal={Blood}, publisher={American Society of Hematology}, author={Scott, C.L. and Hughes, D.A. and Cary, D. and Nicola, N.A. and Begley, C.G. and Robb, L.}, year={1998}, month=dec, pages={4119–4127} }