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Bryostatin 1 modulates the proliferation and lineage commitment of human
myeloid progenitor cells exposed to recombinant interleukin-3 and
recombinant granulocyte-macrophage colony-stimulating factor
F Li, S Grant, GR Pettit and CW McCrady
Division of Hematology/Oncology, Medical College of Virginia, Richmond.
The activity of protein kinase C (PK-C) has been implicated in the
regulation of the growth and differentiation of both normal and neoplastic
hematopoietic cells. We have examined the effects of the PK- C-activating
agents phorbol 12,13-dibutyrate (PDBu), mezerein, and bryostatin 1 on the
proliferation and lineage commitment of CD34+ human myeloid progenitor
cells stimulated by recombinant interleukin-3 (rIL- 3) and/or recombinant
granulocyte-macrophage colony-stimulating factor (rGM-CSF). Although each
of the PK-C activators administered alone induced no colony formation,
coadministration of these agents with plateau concentrations of each
cytokine (eg, 50 ng/mL) increased the number of day 14
granulocyte-macrophage colony-forming units by 100% to 150%. The number of
pure and mixed neutrophil and macrophage colonies was substantially
enhanced in the presence of PK-C activators, whereas the percentage and, in
most cases, the absolute number of eosinophilic colonies was significantly
reduced. The inhibition of eosinophilic colony formation was not overcome
by the addition of rIL-5. Although addition of bryostatin 1 24 hours before
rIL-3 abrogated the increase in total colony formation observed with
simultaneous administration of factors, the inhibition of eosinophilic
colonies and the increase in neutrophil/macrophage colonies persisted under
these conditions. The addition of bryostatin 1 for up to 144 hours after
rIL-3 continued to potentiate total colony formation, whereas the
inhibition of eosinophilic commitment was lost after 120 hours. Together,
these results suggest that pharmacologic interventions at the level of PK-C
may regulate both the proliferation as well as the lineage commitment of
human hematopoietic progenitors exposed to rGM-CSF and rIL-3.
Volume 80,
Issue 10,
pp. 2495-2502,
11/15/1992
Copyright © 1992 by The American Society of Hematology
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