IL-4 promotes macrophage development by rapidly stimulating lineage restriction of bipotent granulocyte-macrophage colony-forming cells.

2.50
Hdl Handle:
http://hdl.handle.net/10541/97416
Title:
IL-4 promotes macrophage development by rapidly stimulating lineage restriction of bipotent granulocyte-macrophage colony-forming cells.
Authors:
Nicholls, S E; Heyworth, Clare M; Dexter, T Michael; Lord, J M; Johnson, G D; Whetton, Anthony D
Abstract:
Granulocyte macrophage colony-forming cells (GM-CFC) are bipotential progenitor cells that can proliferate and develop into macrophages in response to macrophage CSF or into neutrophils in response to stem cell factor or granulocyte CSF. These cytokines promoted growth and development in highly enriched GM-CFC. In [3H]thymidine suicide assays, IL-4 was shown to stimulate proliferation of GM-CFC to the same degree as IL-3 and other potent mitogens for GM-CFC. IL-4 also maintained the clonogenic potential of enriched GM-CFC over a 2-day period. However, after several days in the presence of IL-4, the GM-CFC began to die and retained blast cell morphology characteristic of the isolated GM-CFC. When a high concentration of IL-4 was added to GM-CFC with neutrophilic stimuli, the response of these cells was altered because macrophages were formed. This effect was achieved by a 4-h preincubation with IL-4, suggesting that an early signal produced by IL-4 promotes lineage restriction, although IL-4 itself cannot promote development. IL-4, like macrophage CSF, translocates PKC-alpha to the nucleus in GM-CFC, this redistribution of protein kinase C alpha (PKC-alpha) being inhibited by calphostin C (a PKC inhibitor). Calphostin C also blocked IL-4-mediated development of macrophages in stem cell factor- and granulocyte-CSF-treated cells. This is further evidence that PKC-alpha translocation is involved in the commitment of GM-CFC to macrophage development. This data also suggests that agonist-stimulated lineage commitment can be uncoupled from development in normal hematopoietic cells.
Affiliation:
Department of Biochemistry and Applied Molecular Biology, UMIST, Manchester, United Kingdom.
Citation:
IL-4 promotes macrophage development by rapidly stimulating lineage restriction of bipotent granulocyte-macrophage colony-forming cells. 1995, 155 (2):845-53 J. Immunol.
Journal:
Journal of Immunology
Issue Date:
15-Jul-1995
URI:
http://hdl.handle.net/10541/97416
PubMed ID:
7608562
Type:
Article
Language:
en
ISSN:
0022-1767
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorNicholls, S Een
dc.contributor.authorHeyworth, Clare Men
dc.contributor.authorDexter, T Michaelen
dc.contributor.authorLord, J Men
dc.contributor.authorJohnson, G Den
dc.contributor.authorWhetton, Anthony Den
dc.date.accessioned2010-04-26T14:33:08Z-
dc.date.available2010-04-26T14:33:08Z-
dc.date.issued1995-07-15-
dc.identifier.citationIL-4 promotes macrophage development by rapidly stimulating lineage restriction of bipotent granulocyte-macrophage colony-forming cells. 1995, 155 (2):845-53 J. Immunol.en
dc.identifier.issn0022-1767-
dc.identifier.pmid7608562-
dc.identifier.urihttp://hdl.handle.net/10541/97416-
dc.description.abstractGranulocyte macrophage colony-forming cells (GM-CFC) are bipotential progenitor cells that can proliferate and develop into macrophages in response to macrophage CSF or into neutrophils in response to stem cell factor or granulocyte CSF. These cytokines promoted growth and development in highly enriched GM-CFC. In [3H]thymidine suicide assays, IL-4 was shown to stimulate proliferation of GM-CFC to the same degree as IL-3 and other potent mitogens for GM-CFC. IL-4 also maintained the clonogenic potential of enriched GM-CFC over a 2-day period. However, after several days in the presence of IL-4, the GM-CFC began to die and retained blast cell morphology characteristic of the isolated GM-CFC. When a high concentration of IL-4 was added to GM-CFC with neutrophilic stimuli, the response of these cells was altered because macrophages were formed. This effect was achieved by a 4-h preincubation with IL-4, suggesting that an early signal produced by IL-4 promotes lineage restriction, although IL-4 itself cannot promote development. IL-4, like macrophage CSF, translocates PKC-alpha to the nucleus in GM-CFC, this redistribution of protein kinase C alpha (PKC-alpha) being inhibited by calphostin C (a PKC inhibitor). Calphostin C also blocked IL-4-mediated development of macrophages in stem cell factor- and granulocyte-CSF-treated cells. This is further evidence that PKC-alpha translocation is involved in the commitment of GM-CFC to macrophage development. This data also suggests that agonist-stimulated lineage commitment can be uncoupled from development in normal hematopoietic cells.en
dc.language.isoenen
dc.subjectHaematopoietic Stem Cellsen
dc.subject.meshAnimals-
dc.subject.meshBone Marrow Cells-
dc.subject.meshCell Differentiation-
dc.subject.meshGranulocyte-Macrophage Colony-Stimulating Factor-
dc.subject.meshGranulocytes-
dc.subject.meshHematopoietic Stem Cells-
dc.subject.meshInterleukin-4-
dc.subject.meshMacrophages-
dc.subject.meshMice-
dc.subject.meshProtein Kinase C-
dc.subject.meshSignal Transduction-
dc.subject.meshStem Cells-
dc.subject.meshTranslocation, Genetic-
dc.titleIL-4 promotes macrophage development by rapidly stimulating lineage restriction of bipotent granulocyte-macrophage colony-forming cells.en
dc.typeArticleen
dc.contributor.departmentDepartment of Biochemistry and Applied Molecular Biology, UMIST, Manchester, United Kingdom.en
dc.identifier.journalJournal of Immunologyen
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