| Abstract No.: | C-C3111 |
| Country: | Canada |
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| Title: | A PERIPHERAL ROLE FOR GALECTIN-1: IMPLICATIONS IN AXOTOMY-INDUCED MACROPHAGE ACCUMULATION |
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| Authors/Affiliations: | 4 Andrew Gaudet*; 3 Jami Bennett; 2 Toshihiko Kadoya; 5 Hidenori Horie; 1 Francoise Poirier; 3 Wolfram Tetzlaff; 3 Matt Ramer;
1 Institut Jacques Monod, Pari, France; 2 Kirin Brewery, Gunma, Japan; 3 UBC, Vancouver, BC, Canada; 4 University of British Columbia (UBC), Vancouver, BC, Canada; 5 Waseda University, Tokyo, Japan;
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| Content: | Although axons in the peripheral nervous system have the ability to regrow following injury, their regenerative success is often poor. Efficient degeneration of debris in the injured nerve is necessary for proper peripheral axonal regeneration and is characterized by activation and migration of Schwann cells and infiltration and activation of hematogenous macrophages. Activated macrophages generate myriad cytokines and are especially important in the phagocytosis of inhibitory myelin and axonal debris; thus, these cells are critical in the production of an environment permissive to axonal outgrowth and in the mediation of a robust regenerative response. Numerous cytokines have been implicated in the recruitment/activation of macrophages following peripheral nerve injury. Galectin-1 (Gal1) is a protein that may have cytokine-like effects on macrophages: macrophages exposed to Gal1 express and release an axonal regeneration-promoting factor. Moreover, Gal1 expression in neurons is correlated positively with regenerative potential.
OBJECTIVE:
Determine whether galectin-1 is involved in the accumulation of macrophages following peripheral nerve injury in mouse.
METHODS:
Gal1 wild-type (Lgals1+/+) and null mutant (-/-) mice were used in these experiments. Immunohistochemistry was used to visualize expression of Gal1, F4/80 (macrophage marker), and NIMP-R14 (neutrophil marker). Various neural tissues associated with injury were analyzed for macrophage and neutrophil density at various timepoints following tight ligation of the sciatic nerve. Gal1 or anti-Gal1 were injected into the sciatic nerve, and transplant of sciatic nerves from Lgals1+/+ and -/- mice were used to elucidate the role of Gal1 in accumulation of immune cells.
RESULTS:
Using in vivo models, we have found that Gal1 is involved in the accumulation of macrophages. We demonstrate that exogenous Gal1 is sufficient to facilitate accumulation of macrophages in the uninjured peripheral nerve, and that Gal1 is required for proper macrophage recruitment to various peripheral nervous tissues following sciatic nerve ligation. Gal1 null mutant (Lgals1-/-) mice showed impaired injury-induced recruitment of macrophages to areas associated anatomically with sciatic nerve ligation (the distal sciatic nerve and L5 dorsal root ganglion). Injection of Gal1 into nerves of Lgals1-/- mice was not sufficient to promote accumulation of macrophages, and macrophage responses were impaired following peripheral nerve transplant, suggesting that cytokine cascades are altered in these mice. The density of neutrophils is also reduced after injection of anti-Gal1, suggesting that Gal1 may have a more general role in activating the recruitment of immune cells following peripheral axotomy.
CONCLUSION:
Our data implicate Gal1 in the recruitment of immune cells to the nervous system following peripheral nerve injury and indicate that this protein may affect macrophage chemotaxis indirectly. |
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