A role for Nogo receptor in macrophage clearance from injured peripheral nerve.
We report a role for Nogo receptors (NgRs) in macrophage efflux from sites of inflammation in peripheral nerve. Increasing numbers of macrophages in crushed rat sciatic nerves express NgR1 and NgR2 on the cell surface in the first week after injury. These macrophages show reduced binding to myelin and MAG in vitro, which is reversed by NgR siRNA knockdown and by inhibiting Rho-associated kinase. Fourteen days after sciatic nerve crush, regenerating nerves with newly synthesized myelin have fewer macrophages than cut/ligated nerves that lack axons and myelin. Almost all macrophages in the cut/ligated nerves lie within the Schwann cell basal lamina, while in the crushed regenerating nerves the majority migrate out. Furthermore, crush-injured nerves of NgR1- and MAG-deficient mice and Y-27632-treated rats show impaired macrophage efflux from Schwann cell basal lamina containing myelinated axons. These data have implications for the resolution of inflammation in peripheral nerve and CNS pathologies.
Fry
Elizabeth J
EJ
Center for Research in Neuroscience, The McGill University Health Center, 1650 Cedar Avenue, Montreal, Quebec, Canada.
Ho
Carole
C
David
Samuel
S
D000818:Animals; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D058851:GPI-Linked Proteins; D008024:Ligands; D008264:Macrophages / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D009000:Monocytes / Q000166:cytology; D009185:Myelin Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D009186:Myelin Sheath / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D009409:Nerve Crush; D009410:Nerve Degeneration / Q000276:immunology / Q000473:pathology; D009416:Nerve Regeneration / Q000276:immunology; D009474:Neurons / Q000166:cytology / Q000276:immunology / Q000473:pathology; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; D034741:RNA, Small Interfering; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface; D018000:Receptors, Peptide / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D012583:Schwann Cells / Q000276:immunology / Q000473:pathology / Q000648:ultrastructure; D012584:Sciatic Nerve / Q000276:immunology / Q000293:injuries* / Q000473:pathology
D058851:GPI-Linked Proteins; D008024:Ligands; D009185:Myelin Proteins; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface; D018000:Receptors, Peptide; C000603201:Rtn4 protein, mouse; C000603197:Rtn4 protein, rat; C486581:Rtn4r protein, rat