Enhanced expression of netrin-1 protein in the sciatic nerves of Lewis rats with experimental autoimmune neuritis: possible role of the netrin-1/DCC binding pathway in an autoimmune PNS disorder.
Netrin-1 is a chemotropic factor that plays an important role as a survival factor in the adult nervous system. To investigate whether netrin-1 is involved in autoimmune injury of the peripheral nervous system (PNS), the temporal expression of netrin-1 protein was analyzed in the sciatic nerves of Lewis rats with experimental autoimmune neuritis (EAN). Western blot analysis revealed a significant increase in the level of netrin-1 protein in the sciatic nerves of rats on days 11 to 24 post-immunization (p.i.) compared to controls; netrin-1 expression declined by day 30 p.i. Immunohistochemistry revealed that netrin-1 protein was expressed weakly in Schwann cells and vessels in the sciatic nerves of normal and CFA-immunized control rats. In the sciatic nerves of EAN-affected rats, netrin-1 immunoreactivity was increased mainly in the cell membrane and extracellular matrix of OX42-positive macrophages and S100-positive Schwann cells at the peak and recovery phases of EAN. Moreover, the putative netrin-1 receptor, deleted in colorectal cancer (DCC), was expressed mainly in axons, some macrophages, and Schwann cells in EAN-affected sciatic nerves, although the level of protein expression did not change significantly over the course of EAN. We suggest that a significant increase in netrin-1 expression contributes to host cell survival and axon regeneration to counter autoimmune injury and inflammation, which may play a role in recovery from EAN-induced paralysis.
Moon
Changjong
C
Department of Veterinary Medicine, Cheju National University, Ara-1-dong, Jeju 690-756, South Korea.
Kim
Heechul
H
Ahn
Meejung
M
Jin
Jae-Kwang
JK
Wang
Hongbing
H
Matsumoto
Yoh
Y
Shin
Taekyun
T
D000818:Animals; D015153:Blotting, Western / Q000379:methods; D039481:CD11b Antigen / Q000378:metabolism; D016923:Cell Death / Q000502:physiology; D000075389:DCC Receptor; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D007150:Immunohistochemistry / Q000379:methods; D020287:In Situ Nick-End Labeling / Q000379:methods; D018996:Myelin P2 Protein; D009414:Nerve Growth Factors / Q000378:metabolism*; D000075388:Netrin-1; D010446:Peptide Fragments; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D051381:Rats; D011917:Rats, Inbred Lew; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000502:physiology*; D009418:S100 Proteins / Q000378:metabolism; D012584:Sciatic Nerve / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013997:Time Factors; D025521:Tumor Suppressor Proteins / Q000378:metabolism* / Q000502:physiology*
D039481:CD11b Antigen; D000075389:DCC Receptor; C501912:Dcc protein, rat; D018996:Myelin P2 Protein; D009414:Nerve Growth Factors; C000617354:Ntn1 protein, rat; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011956:Receptors, Cell Surface; D009418:S100 Proteins; D025521:Tumor Suppressor Proteins; C403271:myelin P2 protein (53-78); D000075388:Netrin-1; D010751:Phosphopyruvate Hydratase