M1-and M2-macrophage polarization in thioacetamide (TAA)-induced rat liver lesions; a possible analysis for hepato-pathology
M1-and M2-macrophage polarization in thioacetamide (TAA)-induced rat liver lesions; a possible analysis for hepato-pathology
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DOI：
10.14670/hh-29.10.497
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发表时间：
2014-04-01
影响因子：
2
通讯作者：
Yamate, Jyoji
中科院分区：
文献类型：
--
作者：
Wijesundera, Kavindra Kumara;Izawa, Takeshi;Yamate, Jyoji
“经典活化的巨噬细胞（M1）”和“选择性活化的巨噬细胞（M2）”出现在损伤组织中，控制炎症或重塑。其机制尚不清楚。为了阐明急性肝损伤中M1-/ m2 -巨噬细胞极化，通过单次注射TAA （300 mg/kg BW）分析F344大鼠M1-和m2相关因素，并在注射后（PI）第10小时和第1至10天收集肝脏样本。采用单、双免疫标记法分析巨噬细胞免疫表型。实时RT-PCR分析M1-/ m2相关因素。在PI第10小时（小叶中心病变尚未发生时），M1的ifn - γ、tnf - α、IL-1 β、IL-6和M2的IL-4的表达已经升高，随后在PI第1-3天，随着小叶中心病变的发生和随后的修复性纤维化，M2的IL-10和tgf - β 1的表达也升高。在PI第10小时，CD204（+）和MHC II类+巨噬细胞在完整的门静脉周围/Glisson鞘区增加，同时颗粒酶B+ NK细胞数量增加。第10小时反应细胞可能产生m1相关因子。除了这些巨噬细胞外，在PI第1-3天，损伤的小叶中央区还出现了CD68（+）、CD163（+）巨噬细胞和CD3(+) T细胞；巨噬细胞同时对CD68/MHCⅱ类、CD163/MHCⅱ类、CD68/CD204、CD163/CD204和MHCⅱ类/CD204发生不同程度的反应。虽然CD68（+）和CD163（+）巨噬细胞分别被认为是M1型和m2型，但双标记表明巨噬细胞的免疫表型在损伤区域和随后的纤维化中是可互换的。M1-/ m2 -巨噬细胞模式将有助于分析肝毒性和了解其发病机制。
"Classically activated macrophages (M1)" and " alternatively activated macrophages (M2)", which appear in injured tissues, control either inflammation or remodeling. The mechanism remains unclear. To clarify the M1-/M2-macrophage polarization in acute liver injury, M1- and M2-related factors were analysed in F344 rats by a single injection of TAA (300 mg/kg BW), and liver samples were collected on post injection (PI) hour 10 and days 1 to 10. Macrophage immunophenotypes were analyzed by single and double immunolabeling. M1-/M2-related factors were analyzed by realtime RT-PCR. On PI hour 10 (when centrilobular lesions were not still developed), expressions of IFN-gamma, TNF-alpha, IL-1 beta, and IL-6 for M1, and IL-4 for M2 were already increased, followed by increased expressions of IL-10 and TGF-beta 1 for M2 on PI days 1-3 with development of centrilobular lesions and subsequent reparative fibrosis. On PI hour 10, CD204(+) and MHC class II+ macrophages already increased in the intact periportal/Glisson's sheath regions, accompanied by an increased number of granzyme B+ NK cells. Reactive cells at PI hour 10 might produce M1-related factors. In addition to these macrophages, CD68(+) and CD163(+) macrophages, and CD3(+) T cells appeared in the injured centrilobular region on PI days 1-3; there were macrophages reacting simultaneously to CD68/MHC class II, CD163/MHC class II, CD68/CD204, CD163/CD204, and MHC class II/CD204 in varying degrees. Although CD68(+) and CD163(+) macrophages are regarded as M1- and M2-types, respectively, the double labeling indicated that macrophage immunophenotypes are interchangeable in injured regions and subsequent fibrosis. An M1-/M2-macrophage paradigm would be useful to analyze hepatotoxicity and to understand the pathogenesis.