Document Detail


Adaptive functional differentiation of dendritic cells: integrating the network of extra- and intracellular signals.
MedLine Citation:
PMID:  16527899     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Phenotypic maturation, cytokine secretion, and migration are distinct functional characteristics of dendritic cells (DCs). These functions are independently regulated by a number of extracellular variables, such as type, strength, and persistence of an array of soluble and membrane-bound mediators. Since the exact composition of these variables in response to infection may differ between individuals, the intracellular signaling pathways activated by these extracellular networks may more closely correlate with DC function and predict the course of adaptive immunity. We found that activation of p38 kinase (p38K), extracellular signal-related kinase 1/2 (ERK1/2), and phosphatidylcholine-specific phospholipase C (PC-PLC) enhanced cytokine secretion, whereas p38K, cyclic adenosine monophosphate (cAMP), and PC-PLC enhanced migration. In contrast, phosphatidylinositol 3-kinase (PI3K)/Akt-1 and cAMP inhibited cytokine secretion while ERK1/2 inhibited migration. Migration and cytokine secretion further differed in their sensitivity to inhibition over time. However, although DCs could be manipulated to express migration, cytokine secretion, or both, the level of activation or persistence of intracellular pathway signaling was not predictive. Our results suggest a modular organization of function. We hypothesize that the expression of specific DC functions integrates a large variety of activating and inhibitory variables, and is represented by the formation of a functional unit of molecular networks-the signal response module (SRM). The combined activities of these modules define the functional outcome of DC activation.
Authors:
Thomas Luft; Elena Rodionova; Eugene Maraskovsky; Michael Kirsch; Michael Hess; Christian Buchholtz; Martin Goerner; Max Schnurr; Radek Skoda; Anthony D Ho
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-03-09
Journal Detail:
Title:  Blood     Volume:  107     ISSN:  0006-4971     ISO Abbreviation:  Blood     Publication Date:  2006 Jun 
Date Detail:
Created Date:  2006-06-06     Completed Date:  2006-08-14     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4763-9     Citation Subset:  AIM; IM    
Affiliation:
The German Cancer Research Center, Dept of Molecular Oncology/Hematology, Heidelberg, Germany. thomas.luft@med.uni-heidelberg.de
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MeSH Terms
Descriptor/Qualifier:
1-Phosphatidylinositol 3-Kinase / immunology
Cell Differentiation / immunology*
Cell Movement / immunology*
Cells, Cultured
Cyclic AMP / immunology
Cytokines / immunology
Dendritic Cells / cytology,  immunology*
Humans
Mitogen-Activated Protein Kinase 1 / immunology
Mitogen-Activated Protein Kinase 3 / immunology
Oncogene Protein v-akt / immunology
Signal Transduction / immunology*
Type C Phospholipases / immunology
p38 Mitogen-Activated Protein Kinases / immunology
Chemical
Reg. No./Substance:
0/Cytokines; 60-92-4/Cyclic AMP; EC 2.7.1.137/1-Phosphatidylinositol 3-Kinase; EC 2.7.11.1/Oncogene Protein v-akt; EC 2.7.11.24/Mitogen-Activated Protein Kinase 1; EC 2.7.11.24/Mitogen-Activated Protein Kinase 3; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases; EC 3.1.4.-/Type C Phospholipases; EC 3.1.4.3/phosphatidylcholine-specific phospholipase C

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


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