上海交通大学徐艳艳等研究人员合作发现，血小板中STING的激活通过增强血小板的激活和颗粒的分泌而加剧败血症血栓的形成。这一研究成果于2023年3月20日在线发表在国际学术期刊《免疫》上。

研究人员使用败血症的结扎和穿刺（CLP）模型，通过眼底显微镜观察小鼠血管内的败血症血栓形成和中性粒细胞外陷阱（NETosis）。血小板中的STING激活是败血症诱发病理的一个关键驱动因素。血小板特异性STING的缺失抑制了血小板的激活和颗粒的分泌，从而缓解了败血症引起的小鼠血管内血栓形成和NETosis。从机制上讲，败血症衍生的cGAMP促进了STING与STXBP2的结合，SNARE复合物的组装，颗粒的分泌，以及随后的败血症血栓形成，这可能取决于STING的棕榈酰化。研究人员产生了一种肽，C-ST5，以阻断STING与STXBP2的结合。用C-ST5处理的败血症小鼠显示出血栓的减少。总之，通过STING激活血小板揭示了限制危及生命的败血症介导的凝血病的潜在策略。

据介绍，败血症是全身感染导致的炎症失调的结果。因此，血小板过度激活导致血栓形成和凝血功能障碍，但目前人们对这些过程缺乏足够的了解。

附：英文原文

Title: STING activation in platelets aggravates septic thrombosis by enhancing platelet activation and granule secretion

Author: Mina Yang, Haojie Jiang, Chen Ding, Lin Zhang, Nan Ding, Guoming Li, Fei Zhang, Jing Wang, Liufu Deng, Junling Liu, Yanyan Xu

Issue&Volume: 2023-03-20

Abstract: Sepsis is a dysregulated inflammatory consequence of systemic infection. As a result,excessive platelet activation leads to thrombosis and coagulopathy, but we currentlylack sufficient understanding of these processes. Here, using the cecal ligation andpuncture (CLP) model of sepsis, we observed septic thrombosis and neutrophil extracellulartrap formation (NETosis) within the mouse vasculature by intravital microscopy. STINGactivation in platelets was a critical driver of sepsis-induced pathology. Platelet-specificSTING deficiency suppressed platelet activation and granule secretion, which alleviatedsepsis-induced intravascular thrombosis and NETosis in mice. Mechanistically, sepsis-derivedcGAMP promoted the binding of STING to STXBP2, the assembly of SNARE complex, granulesecretion, and subsequent septic thrombosis, which probably depended on the palmitoylationof STING. We generated a peptide, C-ST5, to block STING binding to STXBP2. Septicmice treated with C-ST5 showed reduced thrombosis. Overall, platelet activation viaSTING reveals a potential strategy for limiting life-threatening sepsis-mediated coagulopathy.

DOI: 10.1016/j.immuni.2023.02.015

Source: https://www.cell.com/immunity/fulltext/S1074-7613(23)00089-4