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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
1999-4-13
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pubmed:abstractText |
Intracellular signals that mediate differentiation of pluripotent hemopoietic progenitors to dendritic cells (DC) are largely undefined. We have previously shown that protein kinase C (PKC) activation (with phorbol ester (PMA) alone) specifically induces differentiation of primary human CD34+ hemopoietic progenitor cells (HPC) to mature DC. We now find that cytokine-driven (granulocyte-macrophage CSF and TNF-alpha) CD34+ HPC-->DC differentiation is preferentially blocked by inhibitors of PKC activation. To further identify intracellular signals and downstream events important in CD34+ HPC-->DC differentiation we have characterized a human leukemic cell line model of this process. The CD34+ myelomonocytic cell line KG1 differentiates into dendritic-like cells in response to granulocyte-macrophage CSF plus TNF-alpha, or PMA (with or without the calcium ionophore ionomycin, or TNF-alpha), with different stimuli mediating different aspects of the process. Phenotypic DC characteristics of KG1 dendritic-like cells include morphology (loosely adherent cells with long neurite processes), MHC I+/MHC IIbright/CD83+/CD86+/CD14- surface Ag expression, and RelB and DC-CK1 gene expression. Functional DC characteristics include fluid phase macromolecule uptake (FITC-dextran) and activation of resting T cells. Comparison of KG1 to the PMA-unresponsive subline KG1a reveals differences in expression of TNF receptors 1 and 2; PKC isoforms alpha, beta I, beta II, and mu; and RelB, suggesting that these components/pathways are important for DC differentiation. Together, these findings demonstrate that cytokine or phorbol ester stimulation of KG1 is a model of human CD34+ HPC to DC differentiation and suggest that specific intracellular signaling pathways mediate specific events in DC lineage commitment.
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD34,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Surface,
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/Macromolecular Substances,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/RELB protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor RelB,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0022-1767
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pubmed:author |
pubmed-author:BlairP JPJ,
pubmed-author:CarlsonL MLM,
pubmed-author:ChuteJ PJP,
pubmed-author:FransozoGG,
pubmed-author:FranzosoGG,
pubmed-author:GUYL PLP,
pubmed-author:GrimesJ LJL,
pubmed-author:HarlanD MDM,
pubmed-author:KaushalSS,
pubmed-author:LECHWW,
pubmed-author:MurilloMM,
pubmed-author:SiebenlistUU,
pubmed-author:SmootD SDS,
pubmed-author:St LouisD CDC,
pubmed-author:WellsM RMR,
pubmed-author:WilliamsA JAJ,
pubmed-author:WoodcockJ BJB
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
162
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3237-48
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:10092775-Adult,
pubmed-meshheading:10092775-Antigens, CD34,
pubmed-meshheading:10092775-Antigens, Surface,
pubmed-meshheading:10092775-Apoptosis,
pubmed-meshheading:10092775-Cell Differentiation,
pubmed-meshheading:10092775-Cell Division,
pubmed-meshheading:10092775-Cell Line,
pubmed-meshheading:10092775-Cytokines,
pubmed-meshheading:10092775-Dendritic Cells,
pubmed-meshheading:10092775-Enzyme Activation,
pubmed-meshheading:10092775-Gene Expression Regulation,
pubmed-meshheading:10092775-Hematopoietic Stem Cells,
pubmed-meshheading:10092775-Humans,
pubmed-meshheading:10092775-Immunophenotyping,
pubmed-meshheading:10092775-Intracellular Fluid,
pubmed-meshheading:10092775-Lymphocyte Activation,
pubmed-meshheading:10092775-Macromolecular Substances,
pubmed-meshheading:10092775-Protein Kinase C,
pubmed-meshheading:10092775-Proto-Oncogene Proteins,
pubmed-meshheading:10092775-Signal Transduction,
pubmed-meshheading:10092775-T-Lymphocytes,
pubmed-meshheading:10092775-Tetradecanoylphorbol Acetate,
pubmed-meshheading:10092775-Transcription Factor RelB,
pubmed-meshheading:10092775-Transcription Factors
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pubmed:year |
1999
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pubmed:articleTitle |
Evidence for distinct intracellular signaling pathways in CD34+ progenitor to dendritic cell differentiation from a human cell line model.
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pubmed:affiliation |
Immune Cell Biology Program, Naval Medical Research Institute, Bethesda, MD 20889, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.
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