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Macrophage/microglia activation factor expression is restricted to lesion-associated microglial cells after brain trauma

Authors

  • Anna Lünemann,

    1. Center for Anatomy, Institute of Cell Biology and Neurobiology, Center for Anatomy, Charité Universitätsmedizin Berlin, Humboldt University, Berlin, Germany
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    • A.L. and O.U. contributed equally to this article.

  • Oliver Ullrich,

    1. Department of Molecular Immunology and Neuroimmunology, Institute of Immunology, Otto-von-Guericke-UniversityMagdeburg, Germany
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    • A.L. and O.U. contributed equally to this article.

  • Antje Diestel,

    1. Center for Anatomy, Institute of Cell Biology and Neurobiology, Center for Anatomy, Charité Universitätsmedizin Berlin, Humboldt University, Berlin, Germany
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  • Thomas Jöns,

    1. Institute of Electron Microscope and Molecular Neuroanatomy, Center for Anatomy, Charité Universitätsmedizin Berlin,Humboldt University, Berlin, Germany
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  • Olaf Ninnemann,

    1. Center for Anatomy, Institute of Cell Biology and Neurobiology, Center for Anatomy, Charité Universitätsmedizin Berlin, Humboldt University, Berlin, Germany
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  • Adam Kovac,

    1. Center for Anatomy, Institute of Cell Biology and Neurobiology, Center for Anatomy, Charité Universitätsmedizin Berlin, Humboldt University, Berlin, Germany
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  • Elena E. Pohl,

    1. Center for Anatomy, Institute of Cell Biology and Neurobiology, Center for Anatomy, Charité Universitätsmedizin Berlin, Humboldt University, Berlin, Germany
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  • Ralf Hass,

    1. Department of Biochemistry and Tumor Biology, Clinic of Obstetrics and Gynecology, Medical School Hannover, Germany
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  • Robert Nitsch,

    Corresponding author
    1. Center for Anatomy, Institute of Cell Biology and Neurobiology, Center for Anatomy, Charité Universitätsmedizin Berlin, Humboldt University, Berlin, Germany
    • Center for Anatomy, Institute of Cell Biology and Neurobiology, Charité Universitätsmedizin Berlin, Humboldt University, Schumannstr. 20-21, 10098 Berlin, Germany
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  • Sven Hendrix

    1. Center for Anatomy, Institute of Cell Biology and Neurobiology, Center for Anatomy, Charité Universitätsmedizin Berlin, Humboldt University, Berlin, Germany
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Abstract

After traumatic brain lesion, microglial cells are rapidly activated, migrate toward the sites of injury, and cause secondary damage that accounts for most of the loss of brain function. In the present study, we have characterized a new macrophage/microglia activation factor (MAF). Using the monocytic cell line U937, we were able to demonstrate that MAF is upregulated after TPA-induced differentiation into macrophages. We have generated a specific antibody against MAF. In BV-2 microglial cells, MAF is partially co-localized with IB4, a classical microglial marker. In addition, we have analyzed the in vivo expression patterns of MAF after entorhinal cortex lesion. We were able to show a substantial upregulation of MAF on selected CD11b+ and IB4+ macrophages/microglial cells in the deafferented hippocampus and in the perilesional region, while no MAF expression was detectable on the contralateral side. Confocal microscopy revealed a lysosome-like expression pattern in BV-2 cells, as well as in ECL-associated macrophages/microglial cells in vivo. Furthermore, we were able to demonstrate that U937 cells with downregulated MAF converted slower and to a significantly reduced extent to the macrophageal phenotype after TPA treatment. In addition, MAF downregulation in BV-2 microglial cells substantially reduced the phagocytotic uptake of dextran beads. Our data indicate that MAF is expressed in selected macrophages/microglial cells around the lesion and in the degenerating hippocampus after ECL. Furthermore, MAF expression in monocytic cells seems to play a functional role in the differentiation to a phagocytosing phenotype and may be, at least partially, required for phagocytotic activity, specifically in lesioned tissue after brain trauma. © 2005 Wiley-Liss, Inc.

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