Prof. Sébastien Gibot, Service de Réanimation Médicale, Hôpital Central, 29 avenue de Lattre de Tassigny, 54035 Nancy Cedex, France, Tel.: +33 383852970, Fax: +33 383858511, E-mail:
Thromb Haemost. 2017 Aug 30;117(9):1772-1781. doi: 10.1160/TH17-03-0156. Epub 2017 Jul 27.
Triggering Receptor Expressed on Myeloid cells-1 (TREM-1) is an immunoreceptor initially known to be expressed on neutrophils and monocytes/macrophages. TREM-1 acts as an amplifier of the inflammatory response during both infectious and aseptic inflammatory diseases. Another member of the TREM family, The Triggering receptor expressed on myeloid cells Like Transcript-1 (TLT-1) is exclusively expressed in platelets and promotes platelet aggregation. As the gene that encodes for TLT-1 is located in the TREM-1 gene cluster, this prompted us to investigate the expression of TREM-1 on platelets. Here we show that TREM-1 is constitutively expressed in α-granules and mobilised at the membrane upon platelet activation. Pharmacologic inhibition of TREM-1 reduces platelet activation as well as platelet aggregation induced by collagen, ADP, and thrombin in human platelets. Aggregation is similarly impaired in platelets from Trem-1 mice. In vivo, TREM-1 inhibition decreases thrombus formation in a carotid artery model of thrombosis and protects mice during pulmonary embolism without excessive bleeding. These findings suggest that TREM-1 inhibition could be useful adducts in antiplatelet therapies.
髓系细胞触发受体-1（TREM-1）最初被认为在中性粒细胞和单核细胞/巨噬细胞上表达，是一种免疫受体。TREM-1 在感染和无菌性炎症疾病期间作为炎症反应的放大器发挥作用。TREM 家族的另一个成员，髓系细胞触发受体样转录物 1（TLT-1）仅在血小板中表达，并促进血小板聚集。由于编码 TLT-1 的基因位于 TREM-1 基因簇中，这促使我们研究 TREM-1 在血小板上的表达。在这里，我们表明 TREM-1 在 α-颗粒中持续表达，并在血小板激活时在膜上动员。TREM-1 的药理学抑制减少了由胶原、ADP 和凝血酶诱导的人血小板的激活和聚集。在 Trem-1 小鼠的血小板中，聚集也受到类似的损害。在体内，TREM-1 抑制可减少血栓形成模型中的血栓形成，并在肺栓塞期间保护小鼠而不会过度出血。这些发现表明，TREM-1 抑制可能在抗血小板治疗中有用。
