Kosyreva A M, Miroshnichenko E A, Makarova O V
Avtsyn Research Institute of Human Morphology of Petrovsky National Research Centre of Surgery, Moscow, Russia.
Peoples' Friendship University of Russia named after Patrice Lumumba, Moscow, Russia.
Arkh Patol. 2024;86(6):82-91. doi: 10.17116/patol20248606182.
The international consensus Sepsis-3 in 2016 defined sepsis as life-threatening organ dysfunction caused by a disruption of the host response to infection. One of the main mechanisms leading to the death of patients with sepsis is an imbalance of the immune response to pathogens. Activation of immune cells, in particular neutrophils, plays a key role in the mechanisms of sepsis. During sepsis, the number of immature neutrophils in the blood increases, PD-L1 neutrophils appear, which have an immunosuppressive function, and the number of Neu1 subtype of neutrophils, characterized by high expression of the NF-kB inhibitor, the chemokine CXCL8, olfactomedine, which regulates the production of cytokines, and myeloperoxidase, increases. When the inflammatory response generalizes, the phagocytic and bactericidal functions of neutrophils are disrupted. An important role in the mechanisms of sepsis is played by the formation of neutrophil extracellular traps, extracellular DNA, and the nuclear non-histone protein HMGB1, which are DAMPs and have proinflammatory activity. The development of approaches to predicting the development and course of sepsis in injuries and infectious and inflammatory diseases based on assessing the functional activity of neutrophils and their phenotype is a promising area of research, in particular approaches to regulating the functioning of neutrophils using miRNA.
2016年国际脓毒症共识Sepsis-3将脓毒症定义为由宿主对感染的反应紊乱引起的危及生命的器官功能障碍。导致脓毒症患者死亡的主要机制之一是对病原体的免疫反应失衡。免疫细胞,特别是中性粒细胞的激活在脓毒症机制中起关键作用。在脓毒症期间,血液中未成熟中性粒细胞的数量增加,出现具有免疫抑制功能的程序性死亡配体1(PD-L1)阳性中性粒细胞,并且以核因子-κB(NF-κB)抑制剂、趋化因子CXCL8、调节细胞因子产生的嗅觉介素和髓过氧化物酶高表达为特征的中性粒细胞Neu1亚型的数量增加。当炎症反应泛化时,中性粒细胞的吞噬和杀菌功能受到破坏。中性粒细胞胞外陷阱、细胞外DNA和核非组蛋白高迁移率族蛋白B1(HMGB1)的形成在脓毒症机制中起重要作用,它们是损伤相关分子模式(DAMPs)并具有促炎活性。基于评估中性粒细胞的功能活性及其表型来预测创伤、感染性和炎症性疾病中脓毒症的发生和病程的方法的开发是一个有前景的研究领域,特别是使用微小RNA(miRNA)调节中性粒细胞功能的方法。