Pervin Munmun, Karim Mohammad Rabiul, Kuramochi Mizuki, Izawa Takeshi, Kuwamura Mitsuru, Yamate Jyoji
1 Laboratory of Veterinary Pathology, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Izumisano City, Osaka, Japan.
Toxicol Pathol. 2018 Jul;46(5):540-552. doi: 10.1177/0192623318776898. Epub 2018 Jun 24.
To investigate the significance of the appearance of hepatic macrophages and expression of inflammatory factors in normal and macrophage-depleted livers, hepatic macrophages were depleted with liposome (Lipo)-encapsulated clodronate (CLD; 50 mg/kg, i.v.) followed by lipopolysaccharide (LPS) administration (0.1 mg/kg, i.p.) in F344 rats (CLD + LPS). Vehicle control rats (Lipo + LPS) received empty-Lipo before LPS. The low dose of LPS did not result in microscopic changes in the liver in either treatment group but did modulate M1 and M2 macrophage activity in Lipo + LPS rats without altering repopulating hepatic macrophages in CLD + LPS rats. LPS treatment in Lipo + LPS rats dramatically increased the M1 (IL-1β, IL-6, TNF-α, and MCP-1) but not M2 macrophage-related factors (IL-4 and CSF-1) compared to CLD + LPS rats. In the CLD + LPS rats, the M2 macrophage-related factors IL-4 and CSF-1 were elevated. In conclusion, low-dose LPS activated hepatic macrophages in rat livers without causing liver injury or stimulating repopulating hepatic macrophages. These data suggest that LPS may alter the liver microenvironment by modulating M1 or M2 macrophage-related inflammatory mediators and macrophage-based hepatotoxicity.
为了研究正常肝脏和巨噬细胞耗竭的肝脏中肝巨噬细胞的出现及炎症因子表达的意义，用脂质体（Lipo）包裹的氯膦酸盐（CLD；50mg/kg，静脉注射）使F344大鼠的肝巨噬细胞耗竭，随后腹腔注射脂多糖（LPS，0.1mg/kg）（CLD+LPS组）。溶剂对照组大鼠（Lipo+LPS组）在注射LPS前接受空脂质体。低剂量的LPS在两个治疗组中均未导致肝脏出现微观变化，但确实调节了Lipo+LPS组大鼠的M1和M2巨噬细胞活性，而未改变CLD+LPS组大鼠中重新填充的肝巨噬细胞。与CLD+LPS组大鼠相比，LPS处理显著增加了Lipo+LPS组大鼠的M1（IL-1β、IL-6、TNF-α和MCP-1）但未增加M2巨噬细胞相关因子（IL-4和CSF-1）。在CLD+LPS组大鼠中，M2巨噬细胞相关因子IL-4和CSF-1升高。总之，低剂量LPS激活了大鼠肝脏中的肝巨噬细胞，而未引起肝损伤或刺激重新填充的肝巨噬细胞。这些数据表明，LPS可能通过调节M1或M2巨噬细胞相关的炎症介质和基于巨噬细胞的肝毒性来改变肝脏微环境。
