Jérémie Lemarié, Amir Boufenzer, Marc Derive, Sébastien Gibot
Service de Réanimation Médicale, Hôpital Central, CHU Nancy, Université de Lorraine, Nancy, France; Inserm UMR_S1116, Faculté de Médecine de Nancy, Université de Lorraine, Vandoeuvre-les-Nancy, France.
INOTREM SA, Nancy, France.
Pharmacol Res. 2015 Oct;100:261-5. doi: 10.1016/j.phrs.2015.07.027. Epub 2015 Aug 28.
Following myocardial ischemia, an intense activation of the immune system occurs that leads to inflammatory cytokines and chemokines production and to the recruitment of neutrophils and mononuclear cells in the infarcted area. Although pro-inflammatory signals initiate the cellular events necessary for scar formation, excessive and prolonged inflammation promotes deleterious cardiac remodeling and dysfunction. The triggering receptor expressed on myeloid cells-1 (TREM-1) is a highly conserved immune-receptor expressed by neutrophils and monocytes that acts as an amplifier of the innate immune response. Blockade of TREM-1 activation protects from hyper-responsiveness and death during severe infections. Here we review the role of TREM-1 in orchestrating the inflammatory response that follows MI. TREM-1 deletion (Trem-1-/-) or modulation by the use of a short inhibitory peptide (LR12) dampens myocardial inflammation, limits leukocyte recruitment, and improves heart function and survival in mice or pigs. Moreover, the soluble form of TREM-1 (sTREM-1) is found in the plasma of patients suffering from an acute MI and its concentration is an independent predictor of death. This suggests that TREM-1 may constitute a new therapeutic target during acute MI.
心肌缺血后，免疫系统会发生强烈激活，导致炎症细胞因子和趋化因子的产生，并促使中性粒细胞和单核细胞募集至梗死区域。尽管促炎信号启动了瘢痕形成所需的细胞事件，但过度且持久的炎症会促进有害的心脏重塑和功能障碍。髓样细胞表达的触发受体-1（TREM-1）是一种由中性粒细胞和单核细胞表达的高度保守的免疫受体，它作为天然免疫反应的放大器发挥作用。阻断TREM-1激活可在严重感染期间防止过度反应和死亡。在此，我们综述了TREM-1在协调心肌梗死后炎症反应中的作用。TREM-1缺失（Trem-1-/-）或使用短抑制肽（LR12）进行调节可减轻心肌炎症，限制白细胞募集，并改善小鼠或猪的心脏功能和存活率。此外，在急性心肌梗死患者的血浆中发现了可溶性TREM-1（sTREM-1），其浓度是死亡的独立预测指标。这表明TREM-1可能成为急性心肌梗死期间的一个新治疗靶点。
