Granulocyte-macrophage colony-stimulating factor antibody suppresses microglial activity

Implications for anti-inflammatory effects in Alzheimer's Disease and multiple sclerosis

P (Hemachandra) Reddy, Maria Manczak, Wei Zhao, Kazuhiro Nakamura, Christopher Bebbington, Geoffrey Yarranton, Peizhong Mao

    Research output: Contribution to journalArticle

    19 Citations (Scopus)

    Abstract

    The objective of our study was to determine granulocyte-macrophage colony-stimulating factor (GM-CSF) activity in the brain following GM-CSF induction. We injected recombinant mouse GM-CSF into the brains of 8-month-old C57BL6 mice via intracerebroventricular injections and studied the activities of microglia, astrocytes, and neurons. We also sought to determine whether an anti-GM-CSF antibody could suppress endogenous microglial activity in the C57BL6 mice and could also suppress microglial activity induced by the recombinant mouse GM-CSF in another group of C57BL6 mice. Using quantitative real-time RT-PCR, we assessed microglial, astrocytic, and neuronal activity by measuring mRNA expression of pro-inflammatory cytokines, GFAP, and the neuronal marker NeuN in the cerebral cortex tissues from C57BL6 mice. We performed immunoblotting and immunohistochemistry of activated microglia in different regions of the brains from control (phosphate-buffered saline-injected C57BL6 mice) and experimental mice (recombinant GM-CSF-injected C57BL6 mice, GM-CSF antibody-injected C57BL6 mice, and recombinant mouse GM-CSF plus anti-GM-CSF antibody-injected C57BL6 mice). We found increased mRNA expression of CD40 (9.75-fold), tumor necrosis factor-alpha (2.1-fold), CD45 (1.73-fold), and CD11c (1.70-fold) in the cerebral cortex of C57BL6 mice that were induced with recombinant GM-CSF, compared with control mice. Further, the anti-GM-CSF antibody suppressed microglia in mice that were induced with recombinant GM-CSF. Our immunoblotting and immunohistochemistry findings of GM-CSF-associated cytokines in C57BL6 mice induced with recombinant GM-CSF, in C57BL6 mice injected with the anti-GM-CSF antibody, and in C57BL6 mice injected with recombinant mouse GM-CSF plus anti-GM-CSF antibody concurred with our real-time RT-PCR findings. These findings suggest that GM-CSF is critical for microglial activation and that anti-GM-CSF antibody suppresses microglial activity in the CNS. The findings from this study may have implications for anti-inflammatory effects of Alzheimer's disease and experimental autoimmune encephalomyelitis mice (a multiple sclerosis mouse model).

    Original languageEnglish (US)
    Pages (from-to)1514-1528
    Number of pages15
    JournalJournal of Neurochemistry
    Volume111
    Issue number6
    DOIs
    StatePublished - Dec 2009

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    Granulocyte-Macrophage Colony-Stimulating Factor
    Multiple Sclerosis
    Alzheimer Disease
    Anti-Inflammatory Agents
    Antibodies
    Microglia
    Brain
    Immunoblotting
    Cerebral Cortex
    Real-Time Polymerase Chain Reaction
    Cytokines
    Immunohistochemistry
    Messenger RNA
    Autoimmune Experimental Encephalomyelitis

    Keywords

    • Astrocytes
    • Cytokines
    • Immunotherapy
    • Inflammation
    • Microglia
    • Neurodegenerative disease

    ASJC Scopus subject areas

    • Biochemistry
    • Cellular and Molecular Neuroscience

    Cite this

    Granulocyte-macrophage colony-stimulating factor antibody suppresses microglial activity : Implications for anti-inflammatory effects in Alzheimer's Disease and multiple sclerosis. / Reddy, P (Hemachandra); Manczak, Maria; Zhao, Wei; Nakamura, Kazuhiro; Bebbington, Christopher; Yarranton, Geoffrey; Mao, Peizhong.

    In: Journal of Neurochemistry, Vol. 111, No. 6, 12.2009, p. 1514-1528.

    Research output: Contribution to journalArticle

    Reddy, P (Hemachandra) ; Manczak, Maria ; Zhao, Wei ; Nakamura, Kazuhiro ; Bebbington, Christopher ; Yarranton, Geoffrey ; Mao, Peizhong. / Granulocyte-macrophage colony-stimulating factor antibody suppresses microglial activity : Implications for anti-inflammatory effects in Alzheimer's Disease and multiple sclerosis. In: Journal of Neurochemistry. 2009 ; Vol. 111, No. 6. pp. 1514-1528.
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    AU - Zhao, Wei

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