title: Functional analysis of mature hematopoietic cells from mice lacking the betac chain of the granulocyte-macrophage colony-stimulating factor receptor.
abstract: Mice with a null mutation of the betac chain of the granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and IL-5 receptors (betac-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 betac-null mice. In addition, we reexamined the roles of the GM-CSF receptor chain and the betac chain in signaling by GM-CSF. Neutrophils and macrophages from betac-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 betac-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 betac-null mice lung pathology, examination of lavage fluid from the lungs of betac-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 betac-null mice were identified as macrophages using immunohistochemistry. Functional analysis showed that these betac-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 betac receptor were unable to perform GM-CSF-mediated hematopoietic cell functions including glucose transport, but responded normally to a range of other ligands.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, The Cooperative Research Centre for Cellular Growth Factors, PO Royal Melbourne Hospital, Victoria, Australia.
authors.forename: C L
authors.initials: CL
authors.lastname: Scott
authors.forename: D A
authors.initials: DA
authors.lastname: Hughes
authors.forename: D
authors.initials: D
authors.lastname: Cary
authors.forename: N A
authors.initials: NA
authors.lastname: Nicola
authors.forename: C G
authors.initials: CG
authors.lastname: Begley
authors.forename: L
authors.initials: L
authors.lastname: Robb
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D051379:Mice; D009154:Mutation; D011956:Receptors, Cell Surface / Q000235:genetics; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D011956:Receptors, Cell Surface; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor