期刊
GLIA
卷 49, 期 1, 页码 158-160出版社
WILEY
DOI: 10.1002/glia.20093
关键词
complement; classical pathway; myelin oligodendrocyte protein
资金
- NIAID NIH HHS [T32AI07041] Funding Source: Medline
- NINDS NIH HHS [NS46032] Funding Source: Medline
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [T32AI007041] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS046032] Funding Source: NIH RePORTER
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 support the conclusion that the contribution of murine complement to the pathogenesis of demyelinating disease is realized via the alternative pathway. (C) 2004 Wiley-Liss, Inc.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据