A role of extracellular histones as mediators of death in sepsis

我们开发了一种夹心ELISA来定量血清或血浆组蛋白H3水平。该酶联免疫吸附测定试剂盒的工作范围为10 ~ 1000μg/L。健康志愿者血浆中未检测到组蛋白H3，但在脓毒症和DIC患者血浆中观察到显著水平。与幸存者相比，非幸存者的这些水平更高。细胞外组蛋白触发血小板聚集，导致肺毛细血管血栓闭塞和随后的小鼠右侧心力衰竭。这些小鼠表现出DIC的症状，包括血小板减少、凝血酶原时间延长、纤维蛋白原减少、纤维蛋白沉积在毛细血管和出血症状。这些发现表明，组蛋白在败血症期间被释放到细胞外空间，并作为致死性血栓性疾病的触发因素。

We developed a sandwich ELISA to quantify serum or plasma histone H3 levels. The working range of this ELISA was 10-1000μg/L. Histone H3 was not detectable in plasma of healthy volunteers, but significant levels were observed in patients with sepsis and DIC. These levels were higher in non-survivors compared to survivors. Extracellular histones triggered platelet aggregation, leading to thrombotic occlusion of pulmonary capillaries and subsequent right-sided heart failure in mice. These mice displayed signs of DIC, including thrombocytopenia, prolonged prothrombin time, decreased fibrinogen, fibrin deposition in capillaries, and bleeding symptoms. These findings indicate that histones are released into the extracellular space during sepsis and act as a trigger for fatal thrombotic disorders.