A role for galectin-1 in the immune response to peripheral nerve injury.
Galectin-1 (Gal1) is a multi-functional protein that has key roles in organismal growth and survival. In the adult nervous system, Gal1 promotes axonal regeneration following peripheral nerve injury. Although the mechanism by which Gal1 promotes regeneration is unclear, previous reports suggested that Gal1 acts indirectly by activating macrophages. An appropriate response of macrophages is crucial for repair of injured nerves: these immune cells remove obstructive axon and myelin debris in the distal nerve. Here we establish a role for Gal1 in the accumulation of immune cells following peripheral axotomy. We used immunohistochemistry to visualize macrophages (F4/80) in wild-type (Lgals1(+/+)) and knockout (Lgals1(-/-)) mouse sciatic nerves following injury and/or manipulation of Gal1 levels. Density of F4/80 immunoreactivity, which peaks around 3 days post-injury, was decreased in Lgals1(+/+) nerves injected with Gal1 antibody. The typical injury-induced peak of macrophage/microglial density was delayed in the sciatic nerves and fifth lumbar dorsal root ganglia of Lgals1(-/-) mice relative to control mice. Injection of oxidized Gal1 into uninjured sciatic nerve promoted the accumulation of macrophages in Lgals1(+/+) nerves. Finally, we used transplants of sciatic nerve to uncover a compensatory mechanism in Lgals1(-/-) mice that allows for macrophage accumulation (albeit delayed and diminished) following axotomy. We conclude that Gal1 is necessary to direct the typical accumulation of macrophages in the injured peripheral nerve, and that Gal1 is sufficient to promote macrophage accumulation in the uninjured nerve of wild-type mice.
Gaudet
Andrew D
AD
ICORD (International Collaboration On Repair Discoveries), Department of Zoology, and Vancouver Coastal Health Research Institute, University of British Columbia, 818 West 8th Avenue, Vancouver, British Columbia, Canada. adg@icord.org
Leung
Margaret
M
Poirier
Françoise
F
Kadoya
Toshihiko
T
Horie
Hidenori
H
Ramer
Matt S
MS
D000818:Animals; D019771:Axotomy; D037483:Galectin 1 / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007111:Immunity, Cellular / Q000502:physiology; D007150:Immunohistochemistry; D008264:Macrophages / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000637:transplantation; D059348:Peripheral Nerve Injuries; D010525:Peripheral Nerves / Q000276:immunology*; D012584:Sciatic Nerve / Q000293:injuries / Q000473:pathology; D014855:Wallerian Degeneration / Q000276:immunology
D037483:Galectin 1