Oxidized Galectin-1 Stimulates Macrophages to Promote Axonal Regeneration in Peripheral Nerves after Axotomy

Hidenori Horie, Toshihiko Kadoya, Naoshi Hikawa, Kazunori Sango, Hiroko Inoue, Kaori Takeshita, Reiko Asawa, Tomoko Hiroi, Manami Sato, Tohru Yoshioka, Yoshihiro Ishikawa

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    94 Citations (Scopus)

    Abstract

    Various neurotrophic factors that promote axonal regeneration have been investigated in vivo, but the signals that prompt neurons to send out processes in peripheral nerves after axotomy are not well understood. Previously, we have shown oxidized galectin-1 (GAL-1/Ox) promotes initial axonal growth after axotomy in peripheral nerves. However, the mechanism by which GAL-1/Ox promotes axonal regeneration remains unclear and is the subject of the present study. To identify possible target cells of GAL-1/Ox, a fluorescently labeled recombinant human GAL-1/Ox (rhGAL-1/Ox) was incubated with DRG neurons, Schwann cells, and intraperitoneal macrophages from adult rats. Only the cell surfaces of intraperitoneal macrophages bound the rhGAL-1/Ox, suggesting that these cells possess a receptor for GAL-1/Ox. Experiments examining tyrosine phosphorylation revealed that rhGAL-1/Ox stimulated changes in signal transduction pathways in these macrophages. These changes caused macrophages to secrete an axonal growth-promoting factor. This was demonstrated when conditioned media of macrophages stimulated with rhGAL-1/Ox in 48 hr culture strongly enhanced axonal regeneration from transected-nerve sites of DRG explants. Furthermore, activated macrophage-conditioned media also improved Schwann cell migration from the transected-nerve sites. From these results, we propose that axonal regeneration occurs in axotomized peripheral nerves as a result of cytosolic reduced galectin-1 being released from Schwann cells and injured axons, which then becomes oxidized in the extracellular space. Oxidized galectin-1 then stimulates macrophages to secrete a factor that promotes axonal growth and Schwann cell migration, thus enhancing peripheral nerve regeneration.

    Original languageEnglish
    Pages (from-to)1873-1880
    Number of pages8
    JournalJournal of Neuroscience
    Volume24
    Issue number8
    DOIs
    Publication statusPublished - 2004 Feb 25

    Keywords

    • Initial regrowth
    • Macrophage
    • Nerve regeneration
    • Oxidized galectin-1
    • Peripheral nerve
    • Schwann cell

    ASJC Scopus subject areas

    • Neuroscience(all)

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  • Cite this

    Horie, H., Kadoya, T., Hikawa, N., Sango, K., Inoue, H., Takeshita, K., Asawa, R., Hiroi, T., Sato, M., Yoshioka, T., & Ishikawa, Y. (2004). Oxidized Galectin-1 Stimulates Macrophages to Promote Axonal Regeneration in Peripheral Nerves after Axotomy. Journal of Neuroscience, 24(8), 1873-1880. https://doi.org/10.1523/JNEUROSCI.4483-03.2004