Murine complement C4 is not required for experimental autoimmune encephalomyelitis

Glia
Laura A BoosScott R Barnum

Abstract

In vitro studies have demonstrated that myelin and myelin-derived proteins activate both the classical and alternative complement pathways. More recently, studies have shown that mice deficient in factor B, a protein required for activation of the alternative pathway, have attenuated experimental autoimmune encephalomyelitis (EAE), the animal model for multiple sclerosis. The relative contribution of the classical pathway to the pathogenesis of EAE has remained unexplored. To address this question, we performed EAE using mice deficient in C4 (C4-/-), a protein required for full activation of the classical pathway. We found that deletion of the C4 gene does not significantly change either the time of onset or the severity and tempo of myelin oligodendrocyte-induced EAE compared with controls with a fully intact complement system. We observed similar levels of cellular infiltration (CD11b+ macrophages and CD3+ T cells) and demyelination in the two kinds of mice. Despite this, ribonuclease protection assays demonstrated a two- to fourfold increase in several pro-inflammatory cytokines in C4-/- mice with EAE, including interleukin-beta (IL-1beta), IL-18, tumor necrosis factor-alpha (TNF-alpha), IP-10, and RANTES. These results supp...Continue Reading

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Citations

Apr 20, 2011·Proceedings of the National Academy of Sciences of the United States of America·Wilhelm J SchwaebleCordula M Stover
Sep 5, 2012·Journal of Neuroinflammation·Mahdia BenkhouchaPatrice H Lalive
Nov 24, 2006·Proceedings of the National Academy of Sciences of the United States of America·Eduard UrichBurkhard Becher
May 1, 2006·Expert Review of Clinical Immunology·Philip F Stahel, Scott R Barnum
Apr 23, 2010·Journal of Neuroimmunology·Gillian IngramB Paul Morgan
Apr 26, 2007·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Zerong YouMichael J Whalen
Sep 13, 2008·Journal of Neurochemistry·Jessy John AlexanderAndrea Joan Tenner
Dec 2, 2008·Clinical and Experimental Immunology·G IngramB P Morgan
Jul 11, 2008·Immunological Reviews·V Michael Holers
Jan 31, 2006·Brain Research Reviews·Scott R Barnum, Alexander J Szalai
Sep 26, 2015·Nature Communications·Masanori A MurayamaYoichiro Iwakura
Jan 29, 2013·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Lorenz C HundgeburthStefanie Kuerten
Nov 27, 2020·Journal of Neuroinflammation·Nicole D Schartz, Andrea J Tenner
Mar 11, 2020·Brain, Behavior, and Immunity·Jennetta W HammondHarris A Gelbard

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