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Protein kinase C activators can interact synergistically with granulocyte
colony-stimulating factor or interleukin-6 to stimulate colony formation
from enriched granulocyte-macrophage colony-forming cells
CM Heyworth, TM Dexter, SE Nicholls and AD Whetton
Department of Experimental Haematology, Paterson Laboratories, Christie
Hospital NHS Trust, Withington, Manchester, UK.
The effects of direct activators of protein kinase C (PKC) (the phorbol
ester tetradecanoyl phorbol myristic acid [TPA] or bryostatin) on the
ability of a highly enriched population of granulocyte-macrophage
colony-forming cells (GM-CFC) to proliferate and develop in soft agar was
assessed. In the absence of colony stimulating factors, the PKC activators
did not stimulate colony formation. However, in the presence of optimal
concentrations of granulocyte colony-stimulating factor (G- CSF) or
interleukin-6 (IL-6), TPA or bryostatin markedly elevated the number of
colonies formed from the GM-CFC. In the absence of TPA, IL-6, and G-CSF,
respectively, both stimulated the formation of about 3% of the colonies
observed when IL-3 was present. When TPA plus G-CSF or IL- 6 were added
together, this figure increased to 48% and 54%, respectively. In both
instances, the types of mature cells formed was altered from colonies of
mature neutrophilic cells to a mixture consisting predominantly of
macrophages with some neutrophils. Similar results were observed when
bryostatin replaced TPA in these assays. When single cell colony-forming
assays were performed, the same results were obtained. The presence of
G-CSF, or IL-6, and the activator of PKC used (TPA or bryostatin) was
required throughout the colony-forming assay for an optimal synergistic
effect to be observed. These data indicate that agents that activate PKC
can promote the proliferation and development of GM-CFC via a synergistic
interaction with G-CSF or IL-6. Furthermore, there is an apparent role for
PKC in development and possibly lineage commitment of GM-CFC.
Volume 81,
Issue 4,
pp. 894-900,
02/15/1993
Copyright © 1993 by The American Society of Hematology
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