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.

2.50
Hdl Handle:
http://hdl.handle.net/10541/100083
Title:
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.
Authors:
Heyworth, Clare M; Dexter, T Michael; Nicholls, Sian E; Whetton, Anthony D
Abstract:
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.
Affiliation:
Department of Experimental Haematology, Paterson Laboratories, Christie Hospital NHS Trust, Withington, Manchester, UK.
Citation:
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. 1993, 81 (4):894-900 Blood
Journal:
Blood
Issue Date:
15-Feb-1993
URI:
http://hdl.handle.net/10541/100083
PubMed ID:
7679006
Type:
Article
Language:
en
ISSN:
0006-4971
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorHeyworth, Clare Men
dc.contributor.authorDexter, T Michaelen
dc.contributor.authorNicholls, Sian Een
dc.contributor.authorWhetton, Anthony Den
dc.date.accessioned2010-06-01T15:12:41Z-
dc.date.available2010-06-01T15:12:41Z-
dc.date.issued1993-02-15-
dc.identifier.citationProtein 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. 1993, 81 (4):894-900 Blooden
dc.identifier.issn0006-4971-
dc.identifier.pmid7679006-
dc.identifier.urihttp://hdl.handle.net/10541/100083-
dc.description.abstractThe 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.en
dc.language.isoenen
dc.subject.meshAnimals-
dc.subject.meshBlotting, Western-
dc.subject.meshBryostatins-
dc.subject.meshColony-Forming Units Assay-
dc.subject.meshDrug Synergism-
dc.subject.meshEnzyme Activation-
dc.subject.meshGranulocyte Colony-Stimulating Factor-
dc.subject.meshGranulocyte-Macrophage Colony-Stimulating Factor-
dc.subject.meshInterleukin-6-
dc.subject.meshLactones-
dc.subject.meshMacrolides-
dc.subject.meshMacrophage Colony-Stimulating Factor-
dc.subject.meshMacrophages-
dc.subject.meshMice-
dc.subject.meshProtein Kinase C-
dc.subject.meshTetradecanoylphorbol Acetate-
dc.titleProtein 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.en
dc.typeArticleen
dc.contributor.departmentDepartment of Experimental Haematology, Paterson Laboratories, Christie Hospital NHS Trust, Withington, Manchester, UK.en
dc.identifier.journalBlooden
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