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Expression and function of the human granulocyte-macrophage colony-
stimulating factor receptor alpha subunit
PT Jubinsky, AS Laurie, DG Nathan, J Yetz-Aldepe and CA Sieff
Division of Pediatric Hematology and Oncology, Children's Hospital, Boston,
MA.
To determine the expression and function of the granulocyte-macrophage
colony-stimulating factor (GM-CSF) receptor alpha chain (GMR alpha) during
hematopoiesis and on leukemic cells, monoclonal antibodies were raised by
immunizing mice with cells expressing high levels of human GMR alpha. A
pool of five antibodies isolated from three different mice was used to
characterize GMR alpha. This antibody pool (anti-GMR alpha)
immunoprecipitated a protein with the expected molecular weight of GMR
alpha from COS cells transiently transfected with the GMR alpha gene. In
factor-dependent cells, GMR alpha existed as a phosphoprotein. However, its
phosphorylation was not stimulated by the presence of GM- CSF. Anti-GMR
alpha inhibited the GM-CSF-dependent growth of cell lines and normal bone
marrow cells and inhibited the binding of iodinated GM- CSF to its
receptor. Cell surface expression of GMR alpha was examined using anti-GMR
alpha and flow cytometry. GMR alpha was readily detectable on both blood
monocytes and neutrophils. In adherence- depleted normal bone marrow, two
separate populations expressed GMR alpha. The most positive cells were
predominantly macrophages, whereas the cells that expressed less GMR alpha
were largely myelocytes and metamyelocytes. A small population of lin-CD34+
or CD34+CD38- cells also expressed GMR alpha, but they were not capable of
significant growth in colony-forming assays. In contrast, the majority of
lin-CD34+ and CD34+CD38- cells were GMR alpha-, yet they produced large
numbers of myeloid and erythroid colonies in the same assay. Malignant
cells from patients with leukemia were also tested for GMR alpha
expression. All of the myeloid leukemias and only rare lymphoid leukemias
surveyed tested positive for GMR alpha. These results show that anti-GMR
alpha is useful for the functional characterization of the GMR alpha and
for the detection of myeloid leukemia and that GMR alpha is expressed on
certain lineages throughout hematopoietic development; however, progenitors
that express the receptor may have a reduced capacity to proliferate in
response to hematopoietic growth factors.
Volume 84,
Issue 12,
pp. 4174-4185,
12/15/1994
Copyright © 1994 by The American Society of Hematology
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