RT Journal Article
SR Electronic
T1 Oxidized Galectin-1 Stimulates Macrophages to Promote Axonal Regeneration in Peripheral Nerves after Axotomy
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 1873
OP 1880
DO 10.1523/JNEUROSCI.4483-03.2004
VO 24
IS 8
A1 Hidenori Horie
A1 Toshihiko Kadoya
A1 Naoshi Hikawa
A1 Kazunori Sango
A1 Hiroko Inoue
A1 Kaori Takeshita
A1 Reiko Asawa
A1 Tomoko Hiroi
A1 Manami Sato
A1 Tohru Yoshioka
A1 Yoshihiro Ishikawa
YR 2004
UL http://www.jneurosci.org/content/24/8/1873.abstract
AB 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.