TREM-1 amplifies inflammation and is a crucial mediator of septic shock
TREM-1 amplifies inflammation and is a crucial mediator of septic shock
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DOI：
10.1038/35074114
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发表时间：
2001-04-26
期刊：
影响因子：
64.8
通讯作者：
Colonna, M
中科院分区：
文献类型：
--
作者：
Bouchon, A;Facchetti, F;Colonna, M
宿主对细菌感染的先天反应主要由中性粒细胞和单核细胞/巨噬细胞介导（1,2）。这些细胞表达模式识别受体（PRRs），结合微生物群共有的保守分子结构（3,4）。刺激PRR信号通路会启动促炎介质的分泌（3,4），从而促进感染因子的消除和组织修复的诱导。细菌感染引起的过度炎症可导致组织损伤和感染性休克（5-9）。在这里，我们发现对微生物产物的炎症反应是通过骨髓细胞(TREM)-1上表达的触发受体介导的途径放大的。TREM-1是一种激活受体，在感染细菌的人体组织中浸润的中性粒细胞和单核细胞中高水平表达。此外，它在微生物脓毒症患者和实验性脂多糖（LPS）诱导休克小鼠的腹膜中性粒细胞中表达上调。值得注意的是，阻断TREM-1可以保护小鼠免受lps诱导的休克，以及由活大肠杆菌或盲肠结扎穿刺引起的微生物败血症。这些结果表明TREM-1在对细菌的急性炎症反应中具有关键功能，并暗示TREM-1可能是感染性休克的潜在治疗靶点。
Host innate responses to bacterial infections are primarily mediated by neutrophils and monocytes/macrophages(1,2). These cells express pattern recognition receptors (PRRs) that bind conserved molecular structures shared by groups of microorganisms(3,4). Stimulation of PRR signalling pathways initiates secretion of proinflammatory mediators(3,4), which promote the elimination of infectious agents and the induction of tissue repair. Excessive inflammation owing to bacterial infections can lead to tissue damage and septic shock(5-9). Here we show that inflammatory responses to microbial products are amplified by a pathway mediated by triggering receptor expressed on myeloid cells (TREM)-1. TREM-1 is an activating receptor expressed at high levels on neutrophils and monocytes that infiltrate human tissues infected with bacteria. Furthermore, it is upregulated on peritoneal neutrophils of patients with microbial sepsis and mice with experimental lipopolysaccaride (LPS)-induced shock. Notably, blockade of TREM-1 protects mice against LPS-induced shock, as well as microbial sepsis caused by live Escherichia coli or caecal ligation and puncture. These results demonstrate a critical function of TREM-1 in acute inflammatory responses to bacteria and implicate TREM-1 as a potential therapeutic target for septic shock.