Department of Cell Biology, Municipal Laboratory for Liver Protection and Regulation of Regeneration, Capital Medical University, No.10 Xitoutiao, You An Men, Beijing, 100069, People's Republic of China.
Immunol Res. 2018 Jun;66(3):414-424. doi: 10.1007/s12026-018-9002-y.
Scavenger receptors, which are expressed on monocyte/macrophages, play a central role in many pathogenic processes. Here, we examined the role of the class D scavenger receptor (CD68) in bone marrow-derived monocyte/macrophages (BMMs) in chronic liver injury. The expression pattern of multiple scavenger receptors in two liver injury models (methionine-choline-deficient and high fat (MCDHF), carbon tetrachloride (CCl)) were analyzed by qRT-PCR. CD68 expression was characterized by flow cytometric analysis, immunofluorescence, and qRT-PCR. A selective monocyte/macrophage toxicant, gadolinium chloride (GdCl) was applied to analyze the function of CD68 in vitro and in vivo. Among the seven examined scavenger receptors (CD68, CD36, CD204, MARCO, LOX1, SREC, and CD163), the mRNA expression of CD68 first got uppermost and continuously increased throughout the entire stage of chronic liver injury, thus attracting our attention. In the injured liver, the percentage of recruited CD68 BMM increased notably, aligning along the developing fibrotic septa, while the proportion of CD68 KC stayed the same compared with that of control mice. In vitro CD68 was highly expressed in primary cultured BMM, and CD68 reduction was triggered by macrophage phagocytosis and apoptosis in the presence of GdCl. In the damaged liver, the recruitment of CD68 BMM and CD68 mRNA expression were reduced by GdCl administration, leading to the attenuation of liver inflammation and fibrosis. Altogether, scavenger receptor CD68 plays a key role in mouse chronic liver injury, which has important implications for the design of anti-fibrotic therapies.
清道夫受体在单核细胞/巨噬细胞上表达，在许多致病过程中发挥核心作用。在这里，我们研究了 D 类清道夫受体（CD68）在骨髓来源的单核细胞/巨噬细胞（BMM）中在慢性肝损伤中的作用。通过 qRT-PCR 分析了两种肝损伤模型（蛋氨酸-胆碱缺乏和高脂肪（MCDHF）、四氯化碳（CCl））中多种清道夫受体的表达模式。通过流式细胞术分析、免疫荧光和 qRT-PCR 来描述 CD68 的表达模式。应用选择性单核细胞/巨噬细胞毒性剂氯化钆（GdCl）来分析 CD68 在体外和体内的功能。在七种检查的清道夫受体（CD68、CD36、CD204、MARCO、LOX1、SREC 和 CD163）中，CD68 的 mRNA 表达首先最高，并在整个慢性肝损伤阶段持续增加，因此引起了我们的注意。在受损的肝脏中，募集的 CD68 BMM 的百分比显著增加，沿着正在发育的纤维性间隔排列，而与对照小鼠相比，CD68 KC 的比例保持不变。在体外，CD68 在原代培养的 BMM 中高度表达，并且在存在 GdCl 的情况下，巨噬细胞吞噬和凋亡会触发 CD68 的减少。在受损的肝脏中，GdCl 给药会减少 CD68 BMM 的募集和 CD68 mRNA 的表达，从而减轻肝脏炎症和纤维化。总之，清道夫受体 CD68 在小鼠慢性肝损伤中起关键作用，这对设计抗纤维化疗法具有重要意义。
