Histone proteins are physiologically involved in DNA packaging and gene regulation but are extracellularly released by neutrophil/monocyte extracellular traps and mediate thrombo-inflammatory pathways, associated to the severity of many human pathologies, including bacterial/fungal sepsis and COVID-19. Prominent and promising laboratory features in classic and viral sepsis emphasize monocyte distribution width (MDW), due to its ability to distinguish and stratify patients at higher risk of critical conditions or death. No data are available on the roles of histones as MDW modifiers. Comparison of MDW index was undertaken by routine hematology analyzer on whole blood samples from patients with COVID-19 and Sepsis. The impact of histones on the MDW characteristics was assessed by the in vitro time-dependent treatment of healthy control whole blood with histones and histones plus lipopolysaccharide to simulate viral and classical sepsis, respectively. We demonstrated the breadth of early, persistent, and significant increase of MDW index in whole blood from healthy subject treated in vitro with histones, highlighting changes similar to those found in vivo in classic and viral sepsis patients. These findings are mechanistically associated with the histone-induced modifications of cell volume, cytoplasmic granularity and vacuolization, and nuclear structure alterations of the circulating monocyte population. Histones may contribute to the pronounced and persistent monocyte alterations observed in both acute classical and viral sepsis. Assessment of the biological impact of circulating histone released during COVID-19 and sepsis on these blood cells should be considered as key factor modulating both thrombosis and inflammatory processes, as well as the importance of neutralization of their cytotoxic and procoagulant activities by several commercially available drugs (e.g., heparins and heparinoids).

中文翻译：

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循环组蛋白有助于单核细胞和 MDW 改变，作为经典和 COVID-19 脓毒症的常见介质

组蛋白在生理上参与 DNA 包装和基因调控，但由中性粒细胞/单核细胞胞外陷阱在细胞外释放并介导血栓炎症通路，这与许多人类病理的严重程度有关，包括细菌/真菌败血症和 COVID-19。经典和病毒性脓毒症的突出和有希望的实验室特征强调单核细胞分布宽度 (MDW)，因为它能够区分和分层处于危急情况或死亡风险较高的患者。没有关于组蛋白作为 MDW 修饰剂作用的数据。通过常规血液分析仪对 COVID-19 和脓毒症患者的全血样本进行 MDW 指数比较。组蛋白对 MDW 特征的影响通过用组蛋白和组蛋白加脂多糖对健康对照全血进行体外时间依赖性治疗来评估，以分别模拟病毒性败血症和经典败血症。我们证明了在体外用组蛋白治疗的健康受试者的全血中 MDW 指数的早期、持续和显着增加的广度，突出了与经典和病毒性脓毒症患者体内发现的相似的变化。这些发现在机制上与组蛋白诱导的细胞体积改变、细胞质粒度和空泡化以及循环单核细胞群的核结构改变有关。组蛋白可能导致在急性经典脓毒症和病毒性脓毒症中观察到的明显和持续的单核细胞改变。