Whetton, A.D., Heyworth, C.M., Nicholls, S.E. et al. (4 more authors) (1994) Cytokine-mediated protein kinase C activation is a signal for lineage determination in bipotential granulocyte macrophage colony-forming cells. Journal of Cell Biology, 125 (3). pp. 651-659. ISSN 0021-9525
Abstract
Granulocyte macrophage colony-forming cells (GM-CFC) have the potential to develop into either macrophages and/or neutrophils. With a highly enriched population of these cells we have found that although GM-CFC are equally responsive to macrophage colony stimulating factor (M-CSF) and stem cell factor (SCF) in terms of DNA synthesis, M-CSF stimulated the development of colonies containing macrophages in soft gel assays, while SCF promoted neutrophilic colony formation. When SCF and M-CSF were combined, mainly macrophage development was stimulated both in soft agar colony-forming assays and liquid cultures. An analysis of some potential signaling mechanisms associated with cytokine-mediated developmental decisions in GM-CFC revealed that M-CSF, but not SCF, was able to chronically stimulate phosphatidylcholine breakdown and diacylglycerol production, indicating that protein kinase C (PKC) may be involved in the action of M-CSF. Furthermore, M-CSF, but not SCF, can increase the levels of PKC alpha (PKC alpha) expression and stimulate the translocation of PKC alpha to the nucleus. When the PKC inhibitor, calphostin C, was added to GM-CFC cultured in M-CSF then predominantly neutrophils were produced, conversely PKC activators added with SCF stimulated macrophage development. The data indicate a role for PKC in M-CSF-stimulated macrophage development from GM-CFC.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 1994 Rockefeller University Press. Reproduced in accordance with the publisher's self-archiving policy. |
Keywords: | Animals; Bone Marrow Cells; Cell Differentiation; Cell Division; Cell Separation; Cells, Cultured; Diglycerides; Enzyme Activation; Hematopoiesis; Hematopoietic Cell Growth Factors; Hematopoietic Stem Cells; In Vitro Techniques; Inositol Phosphates; Macrophage Colony-Stimulating Factor; Macrophages; Mice; Neutrophils; Protein Kinase C; Second Messenger Systems; Stem Cell Factor |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Engineering (Sheffield) > Department of Chemical and Biological Engineering (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 03 Apr 2019 15:32 |
Last Modified: | 03 Apr 2019 20:16 |
Status: | Published |
Publisher: | Rockefeller University Press |
Refereed: | Yes |
Identification Number: | 10.1083/jcb.125.3.651 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:142174 |