The alternative complement pathway revisited.
The alternative complement pathway revisited.
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DOI：
10.1111/j.1582-4934.2008.00350.x
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发表时间：
2008-08
影响因子：
5.3
通讯作者：
Mollnes TE
中科院分区：
文献类型：
--
作者：
Harboe M;Mollnes TE
旁路途径扩增对经典途径和凝集素补体途径的初始特异性激活的最终效果起主要作用，但扩增的定量作用尚未得到充分研究。在人类疾病的实验模型中，其中替代途径的直接激活已经被假定，这种解释需要修改放置在替代放大的更大的作用。我们最近证明，当初始活化对经典途径高度特异时，替代扩增贡献了80 - 90%的C5活化。备解素作为直接启动旁路途径激活的识别因子的最近鉴定，如经典凝集素途径中的C1q和凝集素途径中的甘露糖结合凝集素，引发了对补体反应机制的新兴趣。补体和Toll样受体，包括CD14分子，是先天免疫的两个主要上游识别系统，在包括缺血再灌注损伤和脓毒症在内的许多疾病中促进炎症反应。这些系统作为“双刃剑”，是保护免受微生物入侵，但有害的主机时，激活不当或不受控制。补体和Toll样受体/CD14的联合抑制应作为治疗方案进行探索，以减少脓毒症期间压倒性的破坏性炎症反应。在这方面，应特别考虑替代途径，因为它在脓毒症中不受控制地扩增。替代途径应被视为一个双重系统，即识别途径主要类似于经典和凝集素途径，和放大机制，众所周知，但定量可能比一般公认的更重要。
Alternative pathway amplification plays a major role for the final effect of initial specific activation of the classical and lectin complement pathways, but the quantitative role of the amplification is insufficiently investigated. In experimental models of human diseases in which a direct activation of alternative pathway has been assumed, this interpretation needs revision placing a greater role on alternative amplification. We recently documented that the alternative amplification contributed to 80–90% of C5 activation when the initial activation was highly specific for the classical pathway. The recent identification of properdin as a recognition factor directly initiating alternative pathway activation, like C1q in the classical and mannose-binding lectin in the lectin pathway, initiates a renewed interest in the reaction mechanisms of complement. Complement and Toll-like receptors, including the CD14 molecule, are two main upstream recognition systems of innate immunity, contributing to the inflammatory reaction in a number of conditions including ischaemia-reperfusion injury and sepsis. These systems act as ‘double-edged swords’, being protective against microbial invasion, but harmful to the host when activated improperly or uncontrolled. Combined inhibition of complement and Toll-like receptors/CD14 should be explored as a treatment regimen to reduce the overwhelming damaging inflammatory response during sepsis. The alternative pathway should be particularly considered in this regard, due to its uncontrolled amplification in sepsis. The alternative pathway should be regarded as a dual system, namely a recognition pathway principally similar to the classical and lectin pathways, and an amplification mechanism, well known, but quantitatively probably more important than generally recognized.
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