Functional analysis of mature hematopoietic cells from mice lacking the βc chain of the granulocyte-macrophage colony-stimulating factor receptor

Mice with a null mutation of the beta c chain of the granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and IL-5 receptors (beta c-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 beta c-null mice. In addition, we reexamined the roles of the GM-CSF receptor or chain and the beta c chain in signaling by GM-CSF. Neutrophils and macrophages from beta c-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-gamma and lipopolysaccharide. GM-CSF-mediated augmentation of survival, phagocytosis, and hydrogen-ion production were absent in neutrophils from beta c-null mice. Intirestingly, we were unable to show any ability of the GM-CSF receptor alpha-chain alone to mediate glucose transport in these cells. In keeping with the beta c-null mice lung pathology, examination of lavage fluid from the lungs of beta c-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 beta c-null mice were identified as macrophages using immunohistochemistry. Functional analysis showed that these beta c-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 beta c-receptor were unable to perform GM-CSF-mediated hematopoietic cell functions including glucose transport, but responded normally to a range of other ligands. (C) 1998 by The American Society of Hematology.