Complement activation by isolated myelin: activation of the classical pathway in the absence of myelin-specific antibodies.

Complement activation by isolated myelin: activation of the classical pathway in the absence of myelin-specific antibodies.
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分离髓磷脂的补体激活:在缺乏髓磷脂特异性抗体的情况下激活经典途径。

DOI:
10.1073/pnas.79.10.3290
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发表时间:
1982
影响因子:
11.1
通讯作者:
Shin,ML
Shin,ML
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Vanguri,P;Koski,CL;Silverman,B;Shin,ML

文献摘要

被引文献

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许多中枢神经系统的病理状况涉及髓鞘膜的损伤和移除。关于这种膜损伤的开始和受损组织的处理机制知之甚少。我们感兴趣的是补体(补体的成分被指定为C1、C2、C3等)和髓鞘膜之间的相互作用,以及补体在放大髓鞘损伤和体内受损髓鞘处理中的可能作用,因为补体的激活会产生膜攻击复合物和调理素。在这项研究中,我们发现在缺乏特异性抗体的情况下,分离的大鼠或人髓磷脂消耗补体。补体的激活通过在与髓磷脂孵育的新鲜血清中显示C3裂解来证明。中枢神经系统髓磷脂与缺乏c2的血清孵育不产生C3消耗,只有少量的因子B转化,从而排除了激活的其他途径。通过C1固定和转移试验直接显示了经典途径的参与。髓磷脂与缺乏C2的血清孵育或与纯化的C1孵育后洗涤,含有C1活性,可以溶解抗forssman IgM抗体致敏的携带C4的绵羊红细胞,以及C2和C3-C9。除髓磷脂外的脑组织膜(通过蔗糖密度梯度离心获得的重膜部分)无法激活C1。
Many pathological conditions of the central nervous system involve damage to and removal of myelin membrane. Very little is known about initiation of this membrane damage and the mechanisms of disposal of the damaged tissue. We are interested in the interaction between complement (the components of complement are designated C1, C2, C3, etc.) and myelin membranes and the possible role of complement in amplifying myelin damage and in the disposal of damaged myelin in vivo, because activation of complement generates both membrane-attack complexes and opsonin(s). In this study, we found that isolated rat or human myelin consumes complement in the absence of specific antibodies. Activation of complement was demonstrated by showing C3 cleavage in fresh serum incubated with myelin. Incubation of central nervous system myelin with C2-deficient serum produced no C3 consumption and only minor factor B conversion, thus excluding the alternative pathway of activation. Involvement of the classical pathway was shown directly by the C1 fixation and transfer assay. Myelin incubated with C2-deficient serum or with purified C1 and then washed contained C1 activity that could lyse sheep erythrocytes sensitized with anti-Forssman IgM antibody and carrying C4, together with C2 and C3-C9. Membranes in brain tissues other than myelin (heavy membrane fraction obtained on sucrose density gradient centrifugation) were unable to activate C1.