Document Detail

Phorbol esters induce differentiation of human CD34+ hemopoietic progenitors to dendritic cells: evidence for protein kinase C-mediated signaling.
MedLine Citation:
PMID:  9558069     Owner:  NLM     Status:  MEDLINE    
The intracellular signals that mediate the differentiation of pluripotent hemopoietic progenitors to dendritic cells (DC) are largely undefined. We have found that the phorbol ester PMA by itself induced 47% +/- 8.7% of input human CD34+ hemopoietic progenitors to differentiate into cells with morphology and surface Ag phenotype characteristic of DC by day 7 of culture. Functionally, PMA-generated DC processed and presented whole soluble Ag and also induced resting T cell proliferation and Ag-specific CTL effector function. Unlike cytokine-driven DC differentiation, PMA suppressed proliferation and induced cell death (in part via apoptosis) in cells that did not differentiate to DC. The effects of PMA were blocked by inhibitors of protein kinase C activation, suggesting a central role for this signaling molecule. PMA-mediated signaling also induced expression of the RelB transcription factor, an NF-kappaB family member implicated in DC differentiation. These findings suggest that phorbol esters activate protein kinase C, which then initiates the terminal component of an intracellular signaling pathway(s) involved in the DC differentiation of CD34+ hemopoietic progenitors.
T A Davis; A A Saini; P J Blair; B L Levine; N Craighead; D M Harlan; C H June; K P Lee
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  160     ISSN:  0022-1767     ISO Abbreviation:  J. Immunol.     Publication Date:  1998 Apr 
Date Detail:
Created Date:  1998-05-04     Completed Date:  1998-05-04     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  3689-97     Citation Subset:  AIM; IM    
Immune Cell Biology Program, Stem Cell Biology Branch, Naval Medical Research Institute, Bethesda, MD 20889-5067, USA.
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MeSH Terms
Antigen Presentation / drug effects
Antigens, CD34 / metabolism*
Base Sequence
Cell Differentiation / drug effects
Cells, Cultured
DNA Primers / genetics
Dendritic Cells / cytology,  drug effects*,  immunology*
Enzyme Activation / drug effects
Hematopoietic Stem Cells / cytology,  drug effects*,  immunology*
Lymphocyte Activation
Polymerase Chain Reaction
Protein Kinase C / metabolism
Proto-Oncogene Proteins*
Signal Transduction
T-Lymphocytes / drug effects,  immunology
T-Lymphocytes, Cytotoxic / drug effects,  immunology
Tetradecanoylphorbol Acetate / pharmacology*
Transcription Factor RelB
Transcription Factors / genetics,  metabolism
Reg. No./Substance:
0/Antigens, CD34; 0/DNA Primers; 0/Proto-Oncogene Proteins; 0/RELB protein, human; 0/Transcription Factors; 147337-75-5/Transcription Factor RelB; 16561-29-8/Tetradecanoylphorbol Acetate; EC Kinase C

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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