TLR2 Regulates Complement-Mediated Inflammation Induced by Blood Loss During Hemorrhage.
TLR2 Regulates Complement-Mediated Inflammation Induced by Blood Loss During Hemorrhage.
复制标题
DOI：
10.1097/shk.0000000000000477
复制
发表时间：
2016-01
期刊：
影响因子：
--
通讯作者：
Fleming SD
中科院分区：
文献类型：
--
作者：
Goering J;Pope MR;Fleming SD
失血引起的失血性休克将大部分血液引导到重要器官，极大地减少了流向肠道的血液，导致损伤和炎症。肠道过度炎症反应包括促炎细胞因子和补体激活，但其机制尚不清楚。Toll样受体在先天免疫反应中起重要作用，Toll样受体2(TLR2)在肠缺血/再灌注损伤中起重要作用。我们假设TLR2在失血后的肠炎症反应中起着不可或缺的作用，并使C57BL/6野生型和TLR2-/-小鼠∼失血总量的30%。术后2小时观察肠道损伤和炎症反应。我们证明，与野生型对照组小鼠相比，TLR2-/-小鼠遭受的肠道损伤和炎症较少。重要的是，TLR2调节二十烷类和补体的激活以及IL-12和肿瘤坏死因子α的分泌，表明TLR2和补体在大量失血时相互作用。
Hemorrhagic shock resulting from blood loss directs the majority of the blood to the vital organs, dramatically reducing blood flow to the intestines and resulting in damage and inflammation. The excessive intestinal inflammatory response includes pro-inflammatory cytokines and complement activation, although the mechanism is not clear. Toll-like receptors play a vital role in the innate immune response and toll-like receptor 2 (TLR2) is required for intestinal ischemia/reperfusion-induced injury. We hypothesized that TLR2 plays an integral role in the intestinal inflammatory response after hemorrhage and subjected C57Bl/6 wild type and Tlr2-/- mice to atraumatic loss of ∼30% total blood volume. Two hours after blood removal, the intestinal injury and inflammation were assessed. We demonstrate that compared to wild type control mice, Tlr2-/- mice sustain less intestinal damage and inflammation. Importantly, TLR2 regulated eicosanoid and complement activation andIL-12 and TNFα secretions, indicating interactions between TLR2 and complement in response to significant blood loss.