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GL Gilmore and RK Shadduck
Western Pennsylvania Cancer Institute, Western Pennsylvania Hospital,
Pittsburgh 15224, USA.
Primitive hematopoietic stem cells differentiate into committed progenitors
that are thought to selectively express hematopoietic growth factor
receptor(s), thereby acquiring hematopoietic growth factor responsiveness.
To assess whether hematopoietic stem cells express hematopoietic growth
factor receptors, the progenitor activity of bone marrow (BM) fractions,
isolated by expression of receptors for macrophage/monocyte
colony-stimulating factor (M-CSF), were examined. Recovery of day-12 spleen
colony-forming units (CFU-S) is diminished in both M-CSF receptor-positive
(M-CSFR+) and M-CSFR- fractions, indicating antibody inhibition of day-12
CFU-S. Incubation of BM cells with antibody without fractionation inhibits
50% to 60% of day-12 CFU- S. This inhibition is specific (control
antibodies have no effect) and reversible by removal of bound antibody at
low pH. Incubating BM cells with control or antireceptor antibody does not
affect day-8 CFU-S, which are predominantly erythroid. Treating sublethally
irradiated mice with antibody inhibits endogenous day-12 CFU-S. These
results indicate that some early progenitors express M-CSFRs, and blocking
M-CSFRs inhibits the ability of these progenitors to form colonies,
possibly because of inactivation caused by prolonged receptor blockade.
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| Copyright © 1995 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||