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Blood, Vol. 92 No. 11 (December 1), 1998:
pp. 4119-4127
Functional Analysis of Mature Hematopoietic Cells From Mice Lacking
the  c Chain of the Granulocyte-Macrophage Colony-Stimulating Factor
Receptor
C.L. Scott,
D.A. Hughes,
D. Cary,
N.A. Nicola,
C.G. Begley, and
L. Robb
From The Walter and Eliza Hall Institute of Medical Research, The
Cooperative Research Centre for Cellular Growth Factors, PO Royal
Melbourne Hospital, Victoria, Australia; Rotary Bone Marrow Research
Laboratories Factors, PO Royal Melbourne Hospital, Victoria, Australia;
and the Sir William Dunn School of Pathology, Oxford, UK.
Mice with a null mutation of the  c chain of the
granulocyte-macrophage colony-stimulating factor (GM-CSF),
interleukin-3 (IL-3), and IL-5 receptors (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 c-null mice. In addition, we
reexamined the roles of the GM-CSF receptor  chain and the c
chain in signaling by GM-CSF. Neutrophils and macrophages from
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- and lipopolysaccharide. GM-CSF-mediated
augmentation of survival, phagocytosis, and hydrogen-ion production
were absent in neutrophils from c-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 c-null mice lung pathology, examination of lavage fluid from the lungs of
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 c-null mice were
identified as macrophages using immunohistochemistry. Functional
analysis showed that these 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 c 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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