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    Phosphatidylinostitol-3 kinase and phospholipase C enhance CSF-1-dependent macrophage survival by controlling glucose uptake

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    Authors
    Chang, M.
    Hamilton, J.
    Scholz, G.
    Masendycz, P.
    Macaulay, S.
    Elsegood, Caryn
    Date
    2009
    Type
    Journal Article
    
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    Citation
    Chang, M. and Hamilton, J. and Scholz, G. and Masendycz, P. and Macaulay, S. and Elsegood, C. 2009. Phosphatidylinostitol-3 kinase and phospholipase C enhance CSF-1-dependent macrophage survival by controlling glucose uptake. Cellular Signalling. 21 (9): pp. 1361-1369.
    Source Title
    Cellular Signalling
    DOI
    10.1016/j.cellsig.2009.04.003
    ISSN
    0898-6568
    School
    School of Biomedical Sciences
    URI
    http://hdl.handle.net/20.500.11937/36613
    Collection
    • Curtin Research Publications
    Abstract

    Colony stimulating factor-1 (CSF-1)-dependent macrophages play crucial roles in the development and progression of several pathological conditions including atherosclerosis and breast cancer metastasis. Macrophages in both of these pathologies take up increased amounts of glucose. Since we had previously shown that CSF-1 stimulates glucose uptake by macrophages, we have now investigated whether glucose metabolism is required for the survival of CSF-1-dependent macrophages as well as examined the mechanism by which CSF-1 stimulates glucose uptake. Importantly, we found that CSF-1-induced macrophage survival required metabolism of the glucose taken up in response to CSF-1 stimulation. Kinetic studies showed that CSF-1 stimulated an increase in the number of glucose transporters at the plasma membrane, including Glut1. The uptake of glucose induced by CSF-1 required intact PI3K and PLC signalling pathways, as well as the downstream effectors Akt and PKC, together with a dynamic actin cytoskeleton. Expression of constitutively active Akt partially restored glucose uptake and macrophage survival in the absence of CSF-1, suggesting that Akt is necessary but not sufficient for optimal glucose uptake and macrophage survival. Taken together, these results suggest that CSF-1 regulates macrophage survival, in part, by stimulating glucose uptake via Glut1, and PI3K and PLC signalling pathways. © 2009 Elsevier Inc.

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