The JI
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     
 

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Mead, R. J.
Right arrow Articles by Morgan, B. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mead, R. J.
Right arrow Articles by Morgan, B. P.
The Journal of Immunology, 2002, 168: 458-465.
Copyright © 2002 by The American Association of Immunologists

The Membrane Attack Complex of Complement Causes Severe Demyelination Associated with Acute Axonal Injury1

Richard J. Mead*, Sim K. Singhrao*, James W. Neal{dagger}, H. Lassmann{ddagger} and B. Paul Morgan2,*

Complement Biology Group, Departments of * Medical Biochemistry and {dagger} Pathology, University of Wales College of Medicine, Heath Park, Cardiff, United Kingdom; and {ddagger} Brain Research Institute, University of Vienna, Vienna, Austria

Complement is implicated in pathology in the human demyelinating disease multiple sclerosis and in animal models that mimic the demyelination seen in multiple sclerosis. However, the components of the complement system responsible for demyelination in vivo remain unidentified. In this study, we show that C6-deficient (C6-) PVG/c rats, unable to form the membrane attack complex (MAC), exhibit no demyelination and significantly reduced clinical score in the Ab-mediated experimental autoimmune encephalomyelitis model when compared with matched C6-sufficient (C6+) rats. In C6+ rats, perivenous demyelination appeared, accompanied by abundant mononuclear cell infiltration and axonal injury. Neither demyelination nor axonal damage was seen in C6- rats, whereas levels of mononuclear cell infiltration were equivalent to those seen in C6+ rats. Reconstitution of C6 to C6- rats yielded pathology and clinical disease indistinguishable from that in C6+ rats. We conclude that demyelination and axonal damage occur in the presence of Ab and require activation of the entire complement cascade, including MAC deposition. In the absence of MAC deposition, complement activation leading to opsonization and generation of the anaphylatoxins C5a and C3a is insufficient to initiate demyelination.




This article has been cited by other articles:


Home page
 J. Neurosci.Home page
V. Ramaglia, R. H. M. King, M. Nourallah, R. Wolterman, R. de Jonge, M. Ramkema, M. A. Vigar, S. van der Wetering, B. P. Morgan, D. Troost, et al.
The Membrane Attack Complex of the Complement System Is Essential for Rapid Wallerian Degeneration
J. Neurosci., July 18, 2007; 27(29): 7663 - 7672.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
N. J. Hepburn, A. S. Williams, M. A. Nunn, J. C. Chamberlain-Banoub, J. Hamer, B. P. Morgan, and C. L. Harris
In Vivo Characterization and Therapeutic Efficacy of a C5-specific Inhibitor from the Soft Tick Ornithodoros moubata
J. Biol. Chem., March 16, 2007; 282(11): 8292 - 8299.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
F. Qiao, C. Atkinson, H. Song, R. Pannu, I. Singh, and S. Tomlinson
Complement Plays an Important Role in Spinal Cord Injury and Represents a Therapeutic Target for Improving Recovery following Trauma
Am. J. Pathol., September 1, 2006; 169(3): 1039 - 1047.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurol. Neurosurg. PsychiatryHome page
P Perini, F Ranzato, M Calabrese, L Battistin, and P Gallo
Intrathecal IgM production at clinical onset correlates with a more severe disease course in multiple sclerosis
J. Neurol. Neurosurg. Psychiatry, August 1, 2006; 77(8): 953 - 955.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
E. Alberdi, M. V. Sanchez-Gomez, I. Torre, M. Domercq, A. Perez-Samartin, F. Perez-Cerda, and C. Matute
Activation of kainate receptors sensitizes oligodendrocytes to complement attack.
J. Neurosci., March 22, 2006; 26(12): 3220 - 3228.
[Abstract] [Full Text] [PDF]

Home page
 Arch NeurolHome page
J. Imitola, T. Chitnis, and S. J. Khoury
Insights Into the Molecular Pathogenesis of Progression in Multiple Sclerosis: Potential Implications for Future Therapies
Arch Neurol, January 1, 2006; 63(1): 25 - 33.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
T. S. Kim and S. Perlman
Virus-Specific Antibody, in the Absence of T Cells, Mediates Demyelination in Mice Infected with a Neurotropic Coronavirus
Am. J. Pathol., March 1, 2005; 166(3): 801 - 809.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
T. Niculescu, S. Weerth, F. Niculescu, C. Cudrici, V. Rus, C. S. Raine, M. L. Shin, and H. Rus
Effects of Complement C5 on Apoptosis in Experimental Autoimmune Encephalomyelitis
J. Immunol., May 1, 2004; 172(9): 5702 - 5706.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
S. H. Weerth, H. Rus, M. L. Shin, and C. S. Raine
Complement C5 in Experimental Autoimmune Encephalomyelitis (EAE) Facilitates Remyelination and Prevents Gliosis
Am. J. Pathol., September 1, 2003; 163(3): 1069 - 1080.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
S. Nakashima, Z. Qian, S. Rahimi, B. A. Wasowska, and W. M. Baldwin III
Membrane Attack Complex Contributes to Destruction of Vascular Integrity in Acute Lung Allograft Rejection
J. Immunol., October 15, 2002; 169(8): 4620 - 4627.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Website Copyright © 2002 by The American Association of Immunologists, Inc. All rights reserved.
All Contents Copyright © 2002 by The American Association of Immunologists, Inc. All rights reserved.