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H Mayani, LJ Guilbert, SC Clark and A Janowska-Wieczorek
Department of Medicine, University of Alberta, Edmonton, Canada.
The effects of recombinant human macrophage colony-stimulating factor
(rhCSF-1) in long-term marrow cultures (LTMC) established from normal bone
marrow cells were examined. When added during the first 3 weeks of culture
(every second day, at 15 ng/mL), rhCSF-1 strongly inhibited the growth of
all hematopoietic progenitors analyzed (colony-forming unit- MIX [CFU-MIX],
CFU-granulocyte macrophage [CFU-GM], CFU-M, CFU-G, burst- forming
unit-erythroid). Paralleling the inhibition of progenitors was the complete
loss of adipocytes from the stromal layer of rhCSF-1- treated cultures. The
inhibitory effect of rhCSF-1 correlated in all instances with the
accumulation in the supernatants of these cultures of an activity
(different from CSF-1) that inhibited colony formation in semisolid
cultures. When addition of rhCSF-1 was delayed 3 weeks, its inhibitory
effects were significantly reduced, which correlated with reduced
inhibitory activity detected in the supernatants. Analysis of CSF-1
concentration by radioreceptor assay confirmed that added rhCSF-1 increased
culture CSF-1 levels and showed that the decreased inhibition observed when
rhCSF-1 is added later in culture was not due to decreased CSF-1 levels at
that point. In contrast, the ability of rhCSF-1 to inhibit hematopoiesis
and accumulate inhibitory activity in LTMC correlated with its rate of
utilization, much higher in the first 2 weeks of culture, when the stromal
layer was being established, than later. These observations document the
inhibitory effect of rhCSF-1 on all aspects of hematopoiesis conducted in
cultures that simulate the hematopoietic microenvironment, demonstrate the
importance of accessory/stromal cells in mediating the effects of rhCSF-1
in LTMC, and point to an inhibitory activity as the mediating agent.
This article has been cited by other articles:
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| Copyright © 1991 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||