TROY and LINGO-1 expression in astrocytes and macrophages/microglia in multiple sclerosis lesions.
Nogo constitutes a family of neurite outgrowth inhibitors contributing to a failure of axonal regeneration in the adult central nervous system (CNS). Nogo-A is expressed exclusively on oligodendrocytes where Nogo-66 segment binds to Nogo receptor (NgR) expressed on neuronal axons. NgR signalling requires a coreceptor p75(NTR) or TROY in combination with an adaptor LINGO-1. To characterize the cell types expressing the NgR complex in the human CNS, we studied demyelinating lesions of multiple sclerosis (MS) brains by immunohistochemistry. TROY and LINGO-1 were identified in subpopulations of reactive astrocytes, macrophages/microglia and neurones but not in oligodendrocytes. TROY was up-regulated, whereas LINGO-1 was reduced in MS brains by Western blot. These results suggest that the ternary complex of NgR/TROY/LINGO-1 expressed on astrocytes, macrophages/microglia and neurones, by interacting with Nogo-A on oligodendrocytes, might modulate glial-neuronal interactions in demyelinating lesions of MS.
Satoh
J
J
Department of Bioinformatics, Meiji Pharmaceutical University, Tokyo, Japan. satoj@my-pharm.ac.jp
Tabunoki
H
H
Yamamura
T
T
Arima
K
K
Konno
H
H
D000328:Adult; D000368:Aged; D001253:Astrocytes / Q000378:metabolism*; D015153:Blotting, Western; D002460:Cell Line; D002478:Cells, Cultured; D003711:Demyelinating Diseases / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D017628:Microglia / Q000378:metabolism*; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000378:metabolism* / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009474:Neurons / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
C482293:LINGO1 protein, human; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D018124:Receptors, Tumor Necrosis Factor; C411850:TNFRSF19 protein, human