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The membrane attack complex of complement causes severe demyelination associated with acute axonal injury

Mead, Richard James, Singhrao, Simarjit Kaur, Neal, James William, Lassmann, H. and Morgan, Bryan Paul ORCID: https://orcid.org/0000-0003-4075-7676 2002. The membrane attack complex of complement causes severe demyelination associated with acute axonal injury. Journal of Immunology 168 , pp. 458-465.

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Abstract

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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
ISSN: 0022-1767
Last Modified: 17 Oct 2022 08:28
URI: https://orca.cardiff.ac.uk/id/eprint/250

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