Lysophosphatidylcholine Alleviates Acute Lung Injury by Regulating Neutrophil Motility and Neutrophil Extracellular Trap Formation.

Lysophosphatidylcholine Alleviates Acute Lung Injury by Regulating Neutrophil Motility and Neutrophil Extracellular Trap Formation.
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DOI:
10.3389/fcell.2022.941914
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发表时间:
2022
影响因子:
5.5
通讯作者:
--
中科院分区:
生物学2区
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--
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脓毒症主要由细菌感染引起,并可引起全身炎症,经常导致患者迅速死亡。然而,这种急性全身炎症反应需要从临床判断标准和缓解症状的早期治疗策略的角度进行进一步研究。溶血磷脂酰胆碱(LPC)18:0可缓解脓毒症症状,但相关机制尚不清楚。因此,我们的目的是评估LPC作为小鼠中由脂多糖诱导的肺部急性炎症的治疗性治疗的有效性。采用脂多糖(LPS)诱导小鼠全身炎症反应,研究LPC在急性肺损伤中性粒细胞迁移和免疫应答中的作用。通过采用LPS刺激的LysM-GFP小鼠的双光子活体成像和其他体外和体内测定,我们研究了LPC是否增强了脓毒症的炎症作用。我们还测试了LPC对来自健康对照和脓毒症患者的人中性粒细胞的作用。我们的数据显示LPC处理减少了先天免疫细胞向肺中的浸润。具体而言,LPC改变了中性粒细胞的迁移模式,增强了受损肺的吞噬功效。此外,LPC治疗减少了中性粒细胞胞外陷阱(NET)的释放,这可能会损害发炎器官中的组织并加剧疾病。它还减少了炎症环境下的人中性粒细胞迁移。结果提示,LPC可通过调节中性粒细胞的功能减轻脓毒症引起的肺部炎症。这些发现为LPC治疗作为脓毒症的潜在治疗策略的有益应用提供了证据。
Sepsis is predominantly initiated by bacterial infection and can cause systemic inflammation, which frequently leads to rapid death of the patient. However, this acute systemic inflammatory response requires further investigation from the perspectives of clinical judgment criteria and early treatment strategies for the relief of symptoms. Lysophosphatidylcholine (LPC) 18:0 may relieve septic symptoms, but the relevant mechanism is not clearly understood. Therefore, we aimed to assess the effectiveness of LPC as a therapeutic treatment for acute inflammation in the lung induced by lipopolysaccharide in mice. Systemic inflammation of mice was induced by lipopolysaccharide (LPS) inoculation to investigate the role of LPC in the migration and the immune response of neutrophils during acute lung injury. By employing two-photon intravital imaging of the LPS-stimulated LysM-GFP mice and other in vitro and in vivo assays, we examined whether LPC alleviates the inflammatory effect of sepsis. We also tested the effect of LPC to human neutrophils from healthy control and sepsis patients. Our data showed that LPC treatment reduced the infiltration of innate immune cells into the lung. Specifically, LPC altered neutrophil migratory patterns and enhanced phagocytic efficacy in the damaged lung. Moreover, LPC treatment reduced the release of neutrophil extracellular trap (NET), which can damage tissue in the inflamed organ and exacerbate disease. It also reduced human neutrophil migration under inflammatory environment. Our results suggest that LPC can alleviate sepsis-induced lung inflammation by regulating the function of neutrophils. These findings provide evidence for the beneficial application of LPC treatment as a potential therapeutic strategy for sepsis.
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