Smirnova E V, Krasnova T N, Proskurnina E V, Mukhin N A
M.V. Lomonosov Moscow State University, Moscow, Russia.
M.V. Lomonosov Moscow State University, Moscow, Russia; I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia, Moscow, Russia.
Ter Arkh. 2017;89(12):110-113. doi: 10.17116/terarkh20178912110-113.
Neutrophil dysfunction plays a considerable role.in systemic lupus erythematosus (SLE) The protective function of neutrophils is carried out through various mechanisms: isolation of granular antimicrobial peptides (gAMP), microbial phagocytosis with subsequent degradation via reactive oxygen species inside the phagolysosomes; as well as bactericidal action due to the release of networks from chromatin and gAMP, also called neutrophil extracellular traps (NECTs). The development of neutropenia in SLE has multiple causes, including the formation of antibodies directly to leukocytes; that of neutralizing autoantibodies to the growth factors of neutrophils and cells - myeloid precursors; bone marrow suppression; involvement of neutrophils in the processes of apoptosis and NETosis. Neutrophils in SLE are characterized by reduced phagocytic ability and pathological oxidative activity. In SLE, there is a decrease in the ability to remove the products of neutrophil apoptosis, which is correlated with disease activity. SLE patients are noted to have a higher expression level of the genes specific for low-density granulocytes, an abnormal immature neutrophil population. The impaired processes of formation of NECTs and removal NETosis products play a substantial role in the pathogenesis of SLE. It is shown that the abnormal formation of NECTs also causes endothelial injury and increases the risk of thromboses. The design of novel drugs that act on the specific parts of the formation of NECTs or contribute to their removal from the extracellular environment can propel therapy for SLE and other autoimmune diseases to new heights. There is evidence for further investigations of neutrophil-mediated pathogenetic processes in SLE in order to identify potential therapeutic targets and to understand the mechanisms of action of drugs used in clinical practice.
中性粒细胞功能障碍在系统性红斑狼疮（SLE）中起重要作用。中性粒细胞的保护功能通过多种机制实现：隔离颗粒性抗菌肽（gAMP）；微生物吞噬作用，随后通过吞噬溶酶体内的活性氧进行降解；以及由于染色质和gAMP释放网络（也称为中性粒细胞胞外陷阱，NECTs）而产生的杀菌作用。SLE中中性粒细胞减少的发生有多种原因，包括直接针对白细胞形成抗体；针对中性粒细胞和细胞（髓系前体细胞）生长因子的中和性自身抗体的形成；骨髓抑制；中性粒细胞参与凋亡和NETosis过程。SLE中的中性粒细胞具有吞噬能力降低和病理性氧化活性的特点。在SLE中，清除中性粒细胞凋亡产物的能力下降，这与疾病活动度相关。SLE患者低密度粒细胞特异性基因的表达水平较高，存在异常的未成熟中性粒细胞群体。NECTs形成过程受损和NETosis产物清除受损在SLE发病机制中起重要作用。研究表明，NECTs的异常形成还会导致内皮损伤并增加血栓形成风险。设计作用于NECTs形成特定部位或有助于将其从细胞外环境中清除的新型药物，可推动SLE和其他自身免疫性疾病的治疗达到新高度。有证据表明需要进一步研究SLE中中性粒细胞介导的致病过程，以确定潜在的治疗靶点并了解临床实践中所用药物的作用机制。
