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

• Published in: The Journal of neuroscience Vol. 24; no. 8; pp. 1873 - 1880
• Main Authors: Horie, Hidenori, Kadoya, Toshihiko, Hikawa, Naoshi, Sango, Kazunori, Inoue, Hiroko, Takeshita, Kaori, Asawa, Reiko, Hiroi, Tomoko, Sato, Manami, Yoshioka, Tohru, Ishikawa, Yoshihiro
• Format: Journal Article
• Language: English
• Published: United States Soc Neuroscience 25.02.2004; Society for Neuroscience
• Subjects: Animals; Antibodies - pharmacology; Axons - drug effects; Axons - physiology; Axotomy; Cell Movement - drug effects; Cells, Cultured; Culture Media, Conditioned - pharmacology; Development/Plasticity/Repair; Fluorescent Dyes; Galectin 1 - chemistry; Galectin 1 - pharmacology; Galectin 1 - physiology; Humans; Macrophages, Peritoneal - cytology; Macrophages, Peritoneal - drug effects; Macrophages, Peritoneal - physiology; Mice; Mice, Inbred C57BL; Nerve Regeneration - drug effects; Nerve Regeneration - physiology; Neurons, Afferent - physiology; Neurons, Afferent - ultrastructure; Oxidation-Reduction; Peripheral Nerves - cytology; Peripheral Nerves - growth & development; Peripheral Nerves - physiology; Phosphorylation - drug effects; Rats; Rats, Wistar; Schwann Cells - cytology; Schwann Cells - drug effects; Schwann Cells - physiology
• ISSN: 0270-6474; 1529-2401; 1529-2401
• DOI: 10.1523/JNEUROSCI.4483-03.2004

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.