Deficiency of the complement regulator CD59a enhances disease severity, demyelination and axonal injury in murine acute experimental allergic encephalomyelitis.
There is a growing body of evidence implicating complement and, in particular, the terminal pathway (membrane attack complex; MAC) in inducing demyelination in multiple sclerosis and experimental allergic encephalomyelitis. In this paper, we examined the disease course and pathological changes in mice deficient in the major regulator of MAC assembly, CD59a, during the course of acute experimental allergic encephalomyelitis induced by immunisation with recombinant myelin oligodendrocyte glycoprotein. Disease incidence and severity were significantly increased in CD59a-deficient mice. The extent of inflammation, demyelination and axonal injury were assessed in spinal cord cross-sections from CD59a-deficient and control mice, and all these parameters were enhanced in the absence of CD59a. Areas of myelin loss and axonal damage in CD59a-deficient mice were associated with deposits of MAC, firmly implicating MAC as a cause of the observed injury. These findings are relevant to some types of human demyelination, where abundant deposits of MAC are found in association with pathology.
Mead
Richard James
RJ
Department of Medical Biochemistry and Immunology, University of Wales College of Medicine, Heath Park, Cardiff, UK.
Neal
James William
JW
Griffiths
Mark Raymond
MR
Linington
Christopher
C
Botto
Marina
M
Lassmann
Hans
H
Morgan
Bryan Paul
BP
D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000473:pathology; D018957:CD59 Antigens / Q000235:genetics / Q000378:metabolism*; D002490:Central Nervous System / Q000378:metabolism* / Q000473:pathology; D003711:Demyelinating Diseases / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009186:Myelin Sheath / Q000378:metabolism / Q000473:pathology; D016037:Single-Blind Method
D018957:CD59 Antigens