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Distribution of receptors for granulocyte-macrophage colony-stimulating
factor on immature CD34+ bone marrow cells, differentiating monomyeloid
progenitors, and mature blood cell subsets
AW Wognum, Y Westerman, TP Visser and G Wagemaker
Department of Hematology, Erasmus University, Rotterdam, The Netherlands.
Biotin-labeled granulocyte-macrophage colony-stimulating factor (GM- CSF),
in combination with phycoerythrin-conjugated streptavidin, enabled flow
cytometric analysis of specific cell-surface GM-CSF receptors on rhesus
monkey bone marrow (BM) and peripheral blood (PB) cells. GM-CSF receptors
were readily detected on PB monocytes and neutrophils, but not on
lymphocytes. In BM, GM-CSF receptors were identified on monocyte and
neutrophil precursors and on subsets of cells that expressed the CD34
antigen. CD34+ cells with high GM-CSF- receptor expression coexpressed high
levels of the class II major histocompatibility antigen RhLA-DR, whereas
CD34+/RhLA-DRlow cells, which represent developmentally earlier cells, were
either GM-CSF- receptor negative or expressed GM-CSF receptors at very low
levels. The fluorescence histogram of CD34bright/RhLA-DRdull cells stained
with biotin-GM-CSF showed that at least a fraction of these cells expressed
low levels of GM-CSF receptors. CD34+ cells with high GM-CSF-receptor
expression, purified by cell sorting, did not form colonies in culture or
proliferate in response to GM-CSF. Instead, GM-CSF stimulation resulted in
terminal differentiation into adherent cells, showing that these cells
represented monocyte precursors. A distinct subset of CD34+ cells expressed
GM-CSF receptors at low-to-intermediate levels and proliferated strongly in
the presence of GM-CSF during short-term culture, but produced very few
erythroid or monomyeloid colonies after longer culture periods. Most
colony-forming cells, also those responsive to GM-CSF alone, were recovered
in the subset of CD34+ cells on which GM-CSF receptors were virtually
undetectable. These cells showed weaker proliferation in short-term
proliferation assays than the CD34+/GM-CSF-receptor-intermediate cells,
consistent with an immature phenotype. The results show that
GM-CSF-receptor expression is initiated in a subset of immature,
CD34bright/RhLA-DRdull cells and is progressively increased during
differentiation into mature granulocytes and monocytes. The method used
provides a new way to deplete developmentally early CD34+ cell of
differentiating granulocyte and monocyte precursor cells.
Volume 84,
Issue 3,
pp. 764-774,
08/01/1994
Copyright © 1994 by The American Society of Hematology
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