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Experimental Models of Multiple Sclerosis pp 245–267Cite as

The Role of Complement in EAE

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Abstract

The complement system is an essential effector of the humoral and cellular immunity involved in cytolysis and immune/inflammatory responses. Complement participates in host defence against pathogens by triggering the formation of the membrane attack complex. Complement opsonins (Clq, C3b, iC3b) interact with surface complement receptors to promote phagocytosis while complement anaphylatoxins C3a and C5a initiate local pro-inflammatory responses that, ultimately, contribute to the protection and healing of the host. However, activation of complement to an inappropriate extent has been proposed to promote tissue injury. There is now compelling evidence that complement is implicated in the pathogenesis of several neurological disorders including the human demyelinating disease multiple sclerosis and experimental allergic encephalomyelitis (EAE), an animal model that mimics the demyelination seen in multiple sclerosis. Deposition of complement proteins correlates with areas of demyelination and axonal loss observed in EAE and complement inhibition ameliorates disease. However, the precise mechanisms underlying complement-mediated damage are still largely unknown. The recent use of transgenic animals is beginning to shed light on the relative contributions of the different complement activation pathways in the pathogenesis of experimental demyelination. These studies will provide the basis for the development of novel drugs aiming to inhibit complement in the the central nervous system.

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Authors and Affiliations

  1. Department of Medical Biochemistry and Immunology, University of Wales College of Medicine, Cardiff, CF14 4XX, UK

    Johan van Beek & B. Paul Morgan

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  1. Johan van Beek
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  2. B. Paul Morgan
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  1. Weill Medical College of Cornell University, New York

    Ehud Lavi

  2. Queen’s Medical Centre, University Hospital, Nottingham, UK

    Cris S. Constantinescu

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van Beek, J., Morgan, B.P. (2005). The Role of Complement in EAE. In: Lavi, E., Constantinescu, C.S. (eds) Experimental Models of Multiple Sclerosis. Springer, Boston, MA. https://doi.org/10.1007/0-387-25518-4_12

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