Document Detail

Glycolytic control of adjuvant-induced macrophage survival: role of PI3K, MEK1/2, and Bcl-2.
MedLine Citation:
PMID:  19270084     Owner:  NLM     Status:  MEDLINE    
Uptake by macrophages forms an important part of the mode of action of particulate adjuvants such as oil-in-water emulsions and alum. We have found previously that such adjuvants promote macrophage survival and suggested that this response may contribute to their efficacy. To explore this adjuvant activity further, we have investigated whether oil-in-water emulsion stimulates glucose uptake in macrophages and whether such uptake is relevant to the promotion of survival. We found that oil-in-water emulsion stimulated glucose uptake in a biphasic manner. The first acute phase was independent of mRNA and protein synthesis but appeared to require PI3K activity. In contrast, the second chronic phase was dependent on mRNA and protein synthesis. Importantly, the second phase of glucose uptake required MEK1/2 as well as PI3K activity, indicating that the MEK1/2 pathway can also contribute to cellular glucose uptake. The increased glucose transporter 1 expression during the second phase and long-term survival also appeared to be dependent on PI3K and MEK1/2 signaling pathways. Metabolism of the glucose was required for the emulsion-stimulated survival as well as the increase of prosurvival Bcl-2 transcript levels and maintenance of Bcl-2 protein expression. As transgenic overexpression of Bcl-2 enhances the survival of macrophages in the absence of growth factor, the glycolytic control of Bcl-2 levels may play a central role in emulsion-stimulated macrophage survival. Enhanced glucose uptake by macrophages may therefore be critical to the action of particulate adjuvants.
Margaret Chang; John A Hamilton; Glen M Scholz; Caryn L Elsegood
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-03-06
Journal Detail:
Title:  Journal of leukocyte biology     Volume:  85     ISSN:  1938-3673     ISO Abbreviation:  J. Leukoc. Biol.     Publication Date:  2009 Jun 
Date Detail:
Created Date:  2009-06-02     Completed Date:  2009-06-17     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8405628     Medline TA:  J Leukoc Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  947-56     Citation Subset:  IM    
The University of Melbourne, Royal Melbourne Hospital, Parkville, Victoria 3050, Australia.
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MeSH Terms
1-Phosphatidylinositol 3-Kinase / metabolism*
Adjuvants, Immunologic / pharmacology*
Cell Survival / drug effects
Emulsions / pharmacology
Gene Expression Regulation / drug effects
Glucose / metabolism
Glucose Transporter Type 1 / metabolism
Glycolysis / drug effects*
MAP Kinase Kinase 1 / metabolism
MAP Kinase Kinase 2 / metabolism
Macrophages / cytology*,  drug effects,  enzymology*
Mitogen-Activated Protein Kinase Kinases / metabolism*
Protein Biosynthesis / drug effects
Protein Stability / drug effects
Proto-Oncogene Proteins c-bcl-2 / genetics,  metabolism*
RNA, Messenger / genetics,  metabolism
Transcription, Genetic / drug effects
Reg. No./Substance:
0/Adjuvants, Immunologic; 0/Emulsions; 0/Glucose Transporter Type 1; 0/Proto-Oncogene Proteins c-bcl-2; 0/RNA, Messenger; 0/Slc2a1 protein, mouse; 50-99-7/Glucose; EC 3-Kinase; EC Kinase Kinase 1; EC Kinase Kinase 2; EC Protein Kinase Kinases

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