Galectin-1 regulates initial axonal growth in peripheral nerves after axotomy

The signals that prompt the axons to send out processes in peripheral nerve s after axotomy are not well understood. Here, we report that galectin-1 ca n play an important role in this initial stage. We developed an in vitro ne rve regeneration model that allows us to monitor the initial axon and suppo rt cell outgrowth from the proximal nerve stump, which is comparable to the initial stages of nerve repair. We isolated a factor secreted from COS1 ce lls that enhanced axonal regeneration, and we identified the factor as gale ctin-1. Recombinant human galectin-1 (rhGAL-1) showed the same activity at low concentrations (50 pg/ml) that are two orders of magnitude lower than t hose of lectin activity. A similarly low concentration was also effective i n in vivo experiments of axonal regeneration with migrating reactive Schwan n cells to a grafted silicone tube after transection of adult rat periphera l nerve. Moreover, the application of functional anti-rhGAL-1 antibody stro ngly inhibited the regeneration in vivo as well as in vitro. The same effec t of rhGAL-1 was confirmed in crush/freeze experiments of the adult mouse s ciatic nerve. Because galectin-1 is expressed in the regenerating sciatic n erves as well as in both sensory neurons and motor neurons, we suggest that galectin-1 may regulate initial repair after axotomy. This high activity o f the factor applied under nonreducing conditions suggests that galectin-1 may work as a cytokine, not as a lectin.