Triggering Receptor Expressed on Myeloid Cells-2 Protects against Polymicrobial Sepsis by Enhancing Bacterial Clearance
Triggering Receptor Expressed on Myeloid Cells-2 Protects against Polymicrobial Sepsis by Enhancing Bacterial Clearance
复制标题
骨髓细胞 2 上表达的触发受体通过增强细菌清除来预防多种微生物败血症
DOI：
10.1164/rccm.201211-1967oc
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发表时间：
2013-07-15
影响因子：
24.7
通讯作者：
Fang, XiangMing
中科院分区：
文献类型：
--
作者：
Chen, QiXing;Zhang, Kai;Fang, XiangMing
原理：髓样细胞上表达的触发受体-2 （TREM-2）是一种主要表达于巨噬细胞和单核细胞源性细胞上的细胞表面受体。TREM-2不仅可以调节炎症反应，还可以作为细菌的吞噬受体。然而，TREM-2在脓毒症中的作用尚不清楚。目的：探讨TREM-2在脓毒症中的作用。方法：观察TREM-2在脓毒症患者及盲肠结扎穿刺多微生物脓毒症小鼠模型中的表达情况。用重组小鼠TREM-2阻断TREM-2的作用。在盲肠结扎和穿刺后的不同时间给予过表达TREM-2的骨髓源性骨髓细胞（BMMCs）。测量结果及主要结果：TREM-2在脓毒症患者及脓毒症小鼠中表达上调。多微生物脓毒症中TREM-2表达的动力学与腹膜灌洗液中细菌负荷的动力学相当。阻断TREM-2的作用导致多微生物脓毒症的死亡率和细菌负担显著增加。即使在脓毒症开始4小时后给药，过表达trem -2的bmmc也能显著降低死亡率。然而，将过表达trem -2的bmmc注射到lps挑战的内毒素血症小鼠中并没有提高存活率。TREM-2在多微生物脓毒症中的保护作用与其抗炎特性无关，但它可以增强体内细菌清除。此外，给予过表达trem -2的bmmc可改善器官损伤。结论：TREM-2通过增强细菌清除，在脓毒症的宿主防御反应中发挥重要作用。
Rationale: Triggering receptor expressed on myeloid cells-2 (TREM-2) is a cell surface receptor primarily expressed on macrophages and monocyte-derived cells. TREM-2 not only functions as a regulator of inflammatory response, but also serves as a phagocytic receptor for bacteria. However, the role of TREM-2 in sepsis remains unknown.Objectives: To investigate whether TREM-2 plays a role in sepsis.Methods: The manner of expression of TREM-2 was evaluated in patients with sepsis and in polymicrobial septic mouse model induced by the cecum ligation and puncture approach. Recombinant mouse TREM-2 was used to block the effect of TREM-2. Bone marrow-derived myeloid cells (BMMCs) that overexpress TREM-2 were administrated into septic mice at various times after cecum ligation and puncture.Measurements and Main Results: The expression levels of TREM-2 were up-regulated in patients with sepsis and septic mice. The kinetics of TREM-2 expression in polymicrobial sepsis was comparable with that of bacteria burden in peritoneal lavage fluid. Blocking the effect of TREM-2 resulted in markedly increased mortality and bacterial burden in polymicrobial sepsis. Administration of TREM-2-overexpressing BMMCs significantly reduced the mortality, even when it was administered 4 hours after the initiation of sepsis. However, injection of TREM-2-overexpressing BMMCs into LPS-challenged endotoxemia mice did not improve the survival rate. The protective effect of TREM-2 in polymicrobial sepsis was not associated with its antiinflammatory properties, but it enhanced bacterial clearance in vivo. Furthermore, administration of TREM-2-overexpressing BMMCs improved the organ injury.Conclusions: TREM-2 plays an important role in the host defense response to sepsis by enhancing bacterial clearance.