Chen Guannan, Song Jieqiong, Zhou Yue, Wu Yuanyuan, Yang Chenghang, Wang Yingqin, Zhong Ming
Department of Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.
Shanghai Institute of Infectious Disease and Biosecurity, School of Public Health, Fudan University, Shanghai, China.
J Thorac Dis. 2024 Sep 30;16(9):6024-6036. doi: 10.21037/jtd-24-1098. Epub 2024 Sep 18.
Ethyl palmitate (EP) is known to promote hepatic fetuin-A production and modulate inflammatory responses, but its potential role in lethal endotoxemia and sepsis remains unclear. This study investigates the plasma fetuin-A levels and further evaluates the impact of hepatic fetuin-A induced by EP on systemic inflammation and macrophage polarization in lethal endotoxemia and sepsis.
Blood samples from 55 sepsis patients and 18 non-septic controls with similar age and sex ratio were collected to perform proteomic analyses and identify significantly different proteins. Serum fetuin-A levels in lipopolysaccharide (LPS) induced endotoxemia mice were assayed by enzyme-linked immunosorbent assay (ELISA). The mouse hepatocyte cell (AML-12) was exposed to different concentrations of EP. experiments were conducted in which adult male C57BL/6J mice were given EP with or without intraperitoneal LPS. Fetuin-A was determined via western blot and immunohistochemical staining. Survival rates, lung and liver injury and levels of pro-inflammatory cytokines were also monitored and assessed using histology, real-time quantitative polymerase chain reaction (RT-qPCR) and ELISA. Additionally, the proportion of macrophages and M1/M2 subtypes in the lung and liver tissues were evaluated by flow cytometry.
Our proteomic results revealed that the plasma fetuin-A levels were significantly decreased in sepsis patients compared with non-septic controls. Similarly, the serum fetuin-A levels were also reduced in endotoxemia mice compared with the control group. EP effectively promoted the production of fetuin-A in AML-12 cells and murine liver tissues. Subsequently, activation of fetuin-A by EP dramatically reduced LPS-induced murine mortality, alleviated lung and liver injury, down-regulated pro-inflammatory mediators and macrophage infiltration. Furthermore, EP regulated macrophage polarization from the M1 (CD45CD11bF4/80CD86) to the M2 (CD45CD11bF4/80CD206) subtype in murine liver tissue.
EP-induced production of fetuin-A prevents sepsis and endotoxemia progression by promoting M2 polarization of macrophages.
已知棕榈酸乙酯（EP）可促进肝脏胎球蛋白-A的产生并调节炎症反应，但其在致死性内毒素血症和脓毒症中的潜在作用仍不清楚。本研究调查血浆胎球蛋白-A水平，并进一步评估EP诱导的肝脏胎球蛋白-A对致死性内毒素血症和脓毒症中全身炎症和巨噬细胞极化的影响。
收集55例脓毒症患者和18例年龄和性别比例相似的非脓毒症对照者的血样，进行蛋白质组学分析并鉴定出显著差异的蛋白质。通过酶联免疫吸附测定（ELISA）检测脂多糖（LPS）诱导的内毒素血症小鼠血清中的胎球蛋白-A水平。将小鼠肝细胞（AML-12）暴露于不同浓度的EP。进行实验，对成年雄性C57BL/6J小鼠腹腔注射LPS，同时给予或不给予EP。通过蛋白质印迹法和免疫组织化学染色测定胎球蛋白-A。还使用组织学、实时定量聚合酶链反应（RT-qPCR）和ELISA监测和评估存活率、肺和肝损伤以及促炎细胞因子水平。此外，通过流式细胞术评估肺和肝组织中巨噬细胞及其M1/M2亚型的比例。
我们的蛋白质组学结果显示，与非脓毒症对照者相比，脓毒症患者的血浆胎球蛋白-A水平显著降低。同样，与对照组相比，内毒素血症小鼠的血清胎球蛋白-A水平也降低。EP有效地促进了AML-12细胞和小鼠肝脏组织中胎球蛋白-A的产生。随后，EP激活胎球蛋白-A显著降低了LPS诱导的小鼠死亡率，减轻了肺和肝损伤，下调了促炎介质和巨噬细胞浸润。此外，EP在小鼠肝脏组织中调节巨噬细胞从M1（CD45CD11bF4/80CD86）向M2（CD45CD11bF4/80CD206）亚型的极化。
EP诱导的胎球蛋白-A的产生通过促进巨噬细胞的M2极化来预防脓毒症和内毒素血症的进展。
