Modulation of the triggering receptor expressed on the myeloid cell type 1 pathway in murine septic shock
Modulation of the triggering receptor expressed on the myeloid cell type 1 pathway in murine septic shock
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DOI：
10.1128/iai.74.5.2823-2830.2006
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发表时间：
2006-05-01
影响因子：
3.1
通讯作者：
Lévy, B
中科院分区：
文献类型：
--
作者：
Gibot, S;Buonsanti, C;Lévy, B
髓样细胞1型（TREM-1）上表达的触发受体是一种细胞表面分子，已在人和鼠多形核中性粒细胞和成熟单核细胞上发现。在微生物成分存在的情况下，TREM-1的激活放大了炎症反应，可能是脓毒症初期观察到的高反应性的原因。为了研究TREM-1通路在实验性小鼠脓毒症中的调节作用，我们使用了TREM-1细胞外部分衍生的类似物合成肽。TREM-1配体在实验性腹膜炎小鼠腹膜和外周中性粒细胞上均有表达。TREM-1肽抑制TREM-1对其配体的识别，保护内毒素小鼠免于死亡。在脓毒症大鼠中，TREM-1肽改善了血流动力学状态，减轻了乳酸酸中毒的发展，调节了肿瘤坏死因子α和白细胞介素-1等促炎细胞因子的产生[3]，提高了生存率。这些肽对动脉压力的保护作用部分可以通过减少一氧化氮的产生来解释。这些数据表明，体内调节TREM-1可能是治疗败血症的合适治疗工具。
The triggering receptor expressed on myeloid cell type 1 (TREM-1) is a cell surface molecule that has been identified on both human and murine polymorphonuclear neutrophils and mature monocytes. The activation of TREM-1 in the presence of microbial components amplifies the inflammatory response and may be responsible for the hyperresponsiveness observed during the initial stage of sepsis. To investigate the effect of the modulation of the TREM-1 pathway during experimental murine sepsis, we used analogue synthetic peptides derived from the extracellular moiety of TREM-1. The TREM-1 ligand was expressed on both peritoneal and peripheral neutrophils during experimental peritonitis in mice. The TREM-1 peptides inhibited the recognition by TREM-1 of its ligand and protected endotoxmic mice from death. In septic rats, the TREM-1 peptides improved the hemodynamic status, attenuated the development of lactic acidosis, modulated the production of such proinflammatory cytokines as tumor necrosis factor alpha and interleukin-1[3, and improved survival. The protective effect of these peptides on arterial pressure could partly be explained by a decreased production of nitric oxide. These data suggest that in vivo modulation of TREM-1 might be a suitable therapeutic tool for the treatment of sepsis.