Functional Analysis of Mature Hematopoietic Cells From Mice Lacking the βc Chain of the Granulocyte-Macrophage Colony-Stimulating Factor Receptor

Abstract

Mice 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.