M1/M2-macrophage Polarization-based Hepatotoxicity in D-galactosamine-induced Acute Liver Injury in Rats
M1/M2-macrophage Polarization-based Hepatotoxicity in D-galactosamine-induced Acute Liver Injury in Rats
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DOI：
10.1177/0192623318801574
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发表时间：
2018-10-01
影响因子：
1.5
通讯作者：
Yamate, Jyoji
中科院分区：
文献类型：
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作者：
Rahman, Nahid;Pervin, Munmun;Yamate, Jyoji
D-半乳糖胺（D-GalN）是一种众所周知的肝毒性药物，可导致肝损伤。相反，肝巨噬细胞在维持肝组织完整性方面发挥关键作用。在6周龄的F344大鼠中通过单次腹膜内注射D-GalN（800 mg/kg体重[BW]）诱导的肝损伤中研究巨噬细胞功能。在单次注射（PSI）后8小时和1、2、3和5天检查血液和肝脏样品。PSI第1天和第2天观察到肝脏病变，包括变性/散在凝固性坏死灶、炎性细胞反应和修复性纤维化，表现为血清天冬氨酸转氨酶和丙氨酸转氨酶水平显著升高以及CD 68 M1表达上调（肿瘤坏死因子-α、白细胞介素[IL]-6和干扰素-γ）和CD 163 M2（转化生长因子-β 1、IL-10、单核细胞趋化蛋白-1和IL-4）巨噬细胞相关因子。PSI第2天的双重免疫荧光染色表明，82%的肝巨噬细胞同时表达CD 163/CD 68; 65-75%的MHC II类巨噬细胞显示CD 163或CD 68的共表达，95%的表达CD 204的巨噬细胞与CD 163或CD 68反应。这些发现表明，M1-和M2-巨噬细胞都有助于D-GalN诱导的肝脏病变的发展，并提供了有关巨噬细胞活化的信息，表明基于M1/M2-极化分析巨噬细胞表型对肝毒性的重要性。
D-galactosamine (D-GalN) is a well-known hepatotoxic agent that causes liver injury. Conversely, hepatic macrophages play a crucial role in maintaining liver tissue integrity. Macrophage functions were investigated in hepatic lesions induced by a single intraperitoneal injection of D-GalN (800 mg/kg body weight [BW]) in 6-week-old F344 rats. Blood and liver samples were examined at 8 hr and on 1, 2, 3, and 5 days postsingle injection (PSI). Hepatic lesions consisting of degeneration/sporadic foci of coagulation necrosis, inflammatory cell reaction, and reparative fibrosis were seen on PSI days 1 and 2, reflected by significantly increased serum levels of aspartate transaminase and alanine transaminase and upregulation of CD68 M1 (tumor necrosis factor-alpha, interleukin [IL]-6, and interferon-gamma) and CD163 M2 (transforming growth factor-beta 1, IL-10, monocyte chemoattractant protein-1, and IL-4) macrophage-related factors. Double immunofluorescence staining on PSI day 2 demonstrated that 82% of hepatic macrophages expressed of CD163/CD68 simultaneously; 65-75% of MHC class II macrophages showed co-expression of CD163 or CD68 and 95% CD204-expressing macrophages reacted to CD163 or CD68. These findings showed that both M1- and M2-macrophages contributed to the development of hepatic lesions induced by D-GalN and provided information about macrophage activation, indicating the importance of analysis of macrophage phenotypes for hepatotoxicity based on M1/M2-polarization.