Requirement of myeloid cells for axon regeneration.
The role of CD11b+ myeloid cells in axonal regeneration was assessed using axonal injury models and CD11b-TK(mt-30) mice expressing a mutated HSV-1 thymidine kinase (TK) gene regulated by the myeloid-specific CD11b promoter. Continuous delivery of ganciclovir at a sciatic nerve lesion site greatly decreased the number of granulocytes/inflammatory monocytes and macrophages in the distal stump of CD11b-TK(mt-30) mice. Axonal regeneration and locomotor function recovery were severely compromised in ganciclovir-treated CD11b-TK(mt-30) mice. This was caused by an unsuitable growth environment rather than an altered regeneration capacity of neurons. In absence of CD11b+ cells, the clearance of inhibitory myelin debris was prevented, neurotrophin synthesis was abolished, and blood vessel formation/maintenance was severely compromised in the sciatic nerve distal stump. Spinal cord-injured axons also failed to regenerate through peripheral nerve grafts in the absence of CD11b+ cells. Therefore, myeloid cells support axonal regeneration and functional recovery by creating a growth-permissive milieu for injured axons.
Barrette
Benoit
B
Department of Anatomy and Physiology, Laval University, Ste-Foy, Québec G1V4G2, Canada.
Hébert
Marc-André
MA
Filali
Mohammed
M
Lafortune
Kathleen
K
Vallières
Nicolas
N
Gowing
Geneviève
G
Julien
Jean-Pierre
JP
Lacroix
Steve
S
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D018845:CD11 Antigens / Q000276:immunology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D015774:Ganciclovir / Q000494:pharmacology; D006085:Graft Survival / Q000502:physiology; D006098:Granulocytes / Q000187:drug effects / Q000276:immunology; D020439:Growth Cones / Q000276:immunology* / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D022423:Myeloid Cells / Q000276:immunology*; D009416:Nerve Regeneration / Q000276:immunology*; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D020426:Sciatic Neuropathy / Q000276:immunology / Q000503:physiopathology; D013937:Thymidine Kinase / Q000235:genetics / Q000276:immunology; D016378:Tissue Transplantation
D000998:Antiviral Agents; D018845:CD11 Antigens; D013937:Thymidine Kinase; D015774:Ganciclovir
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