Cutting edge: An endogenous pathway to systemic inflammatory response syndrome (SIRS)-Like reactions through toll-like receptor 4
Cutting edge: An endogenous pathway to systemic inflammatory response syndrome (SIRS)-Like reactions through toll-like receptor 4
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DOI：
10.4049/jimmunol.172.1.20
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发表时间：
2004-01-01
影响因子：
4.4
通讯作者：
Platt, JL
中科院分区：
文献类型：
--
作者：
Johnson, GB;Brunn, GJ;Platt, JL
全身炎症反应综合征（SIRS）通常与创伤、手术或急性胰腺炎相关。SIRS类似于脓毒症，由作用于Toll样受体的外源性大分子如脂多糖触发。然而，在无感染情况下是什么引发SIRS尚不清楚。在这项研究中，我们报道通过给予可溶性硫酸乙酰肝素（一种与有核细胞和细胞外基质相关的糖胺聚糖）以及弹性蛋白酶（其切割并释放硫酸乙酰肝素蛋白聚糖）可在小鼠中诱导出一种类似SIRS的反应。硫酸乙酰肝素和弹性蛋白酶诱导SIRS的能力取决于功能性Toll样受体4，因为缺乏该受体或其功能的突变小鼠没有反应。这些结果为SIRS的起始提供了一种分子层面的解释。
Systemic inflammatory response syndrome (SIRS) is typically associated with trauma, surgery, or acute pancreatitis. SIRS resembles sepsis, triggered by exogenous macromolecules such as LPS acting on Toll-like receptors. What triggers SIRS in the absence of infection, however, is unknown. In this study, we report that a SIRS-like response can be induced in mice by administration of soluble heparan sulfate, a glycosaminoglycan associated with nucleated cells and extracellular matrices, and by elastase, which cleaves and releases heparan sulfate proteoglycans. The ability of heparan sulfate and elastase to induce SIRS depends on functional Toll-like receptor 4, because mutant mice lacking that receptor or its function do not respond. These results provide a molecular explanation for the initiation of SIRS.