Cutting edge: Targeted disruption of the C3a receptor gene demonstrates a novel protective anti-inflammatory role for C3a in endotoxin-shock
Cutting edge: Targeted disruption of the C3a receptor gene demonstrates a novel protective anti-inflammatory role for C3a in endotoxin-shock
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DOI：
10.4049/jimmunol.165.10.5406
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发表时间：
2000-11-15
影响因子：
4.4
通讯作者：
Wetsel, RA
中科院分区：
文献类型：
--
作者：
Kildsgaard, J;Hollmann, TJ;Wetsel, RA
补体过敏毒素C3 a在结合C3 aR时介导许多促炎活性。此外，最近的体外研究与C3 a有牵连C3 aR作为一种可能的抗炎受体。由于C3 aR在调节炎症反应中可能具有双重作用，因此C3 aR是否参与内毒素休克的发病机制尚不确定。本文报道了小鼠C3 aR的靶向破坏。这些小鼠表现出对内毒素休克的增强的致死性，具有显著的基因剂量效应。此外，在LPS攻击后，与其同窝小鼠相比，C3 aR（-/-）小鼠中LL-1 β的血浆浓度显著升高。这些研究结果表明，C3 aR在内毒素休克中具有重要的保护作用，并表明，除了其传统上被接受的介导炎症的功能外，C3 aR还通过减弱LPS诱导的促炎细胞因子的产生而在体内作为抗炎受体发挥作用。
The complement anaphylatoxin C3a, on binding the C3aR, mediates numerous proinflammatory activities. In addition, recent in vitro studies with C3a have implicated C3aR as a possible anti-inflammatory receptor. Because of its possible dual role in modulating the inflammatory response, it is uncertain whether C3aR contributes to the pathogenesis of endotoxin shock. Here, the targeted-disruption of the C3aR in mice is reported, These mice exhibit an enhanced lethality to endotoxin shock with a pronounced gene dosage effect, In addition, the plasma concentration of LL-1 beta was significantly elevated in the C3aR(-/-) mice compared with their littermates following LPS challenge. These findings demonstrate an important protective role for the C3aR in endotoxin shock and indicate that, in addition to its traditionally accepted functions in mediating inflammation, the C3aR also acts in vivo as an anti-inflammatory receptor by attenuating LPS-induced proinflammatory cytokine production.