FUNCTIONAL-ANALYSIS OF MATURE HEMATOPOIETIC-CELLS FROM MICE LACKING THE BETA-C CHAIN OF THE GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR-RECEPTOR

Mice with a null mutation of the beta c chain of the granulocyte-macro phage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and IL -5 receptors (beta c-null mice) develop an alveolar proteinosis-like l ung disease. The pathogenesis of this disease is uncertain and, althou gh a defect in alveolar macrophage function has been postulated, no pr evious analysis of mature hematopoietic cells in mice with alveolar pr oteinosis has been reported. Therefore, we undertook a functional anal ysis 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 macrophag es from beta c-null mice were capable of normal survival and phagocyto sis in the absence of stimulus and of similar levels of nitric oxide p roduction in response to interferon-gamma and lipopolysaccharide. GM-C SF-mediated augmentation of survival, phagocytosis, and hydrogen-ion p roduction were absent in neutrophils from beta c-null mice. Intirestin gly, we were unable to show any ability of the GM-CSF receptor alpha-c hain alone to mediate glucose transport in these cells. In keeping wit h the beta c-null mice lung pathology, examination of lavage fluid fro m 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 mi ce were identified as macrophages using immunohistochemistry. Function al analysis showed that these beta c-null alveolar macrophages were ca pable of phagocytosis but uptake of colloidal carbon and cellular adhe sion 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 respond ed normally to a range of other ligands. (C) 1998 by The American Soci ety of Hematology.