Chronic alcohol ingestion modulates hepatic macrophage populations and functions in mice
Chronic alcohol ingestion modulates hepatic macrophage populations and functions in mice
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DOI：
10.1189/jlb.6a0114-004rr
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发表时间：
2014-10-01
影响因子：
5.5
通讯作者：
Ju, Cynthia
中科院分区：
文献类型：
--
作者：
Wang, Meng;You, Qiang;Ju, Cynthia
肝 Mac 由驻留 KC 和浸润单核细胞/IM 组成，被认为在 ALD 的发病机制中发挥重要作用。之前的工作主要集中在 KC 或将肝 Mac 作为一个细胞群进行研究。当前研究的目的是区分 IM 和 KC 并比较它们的表型和功能。我们在此表明，对 C57BL/6J 小鼠进行 4 周的乙醇喂养会导致 IM 募集到肝脏中。 KC 和 IM 可以根据 F4/80 和 CD11b 的差异表达来区分。根据 Ly6C 的差异表达，IM 可以进一步分为两个子集。 KC 和 IM 的两个子集分别通过 FACS 纯化。比较不同肝Mac群体的吞噬能力和各种功能相关基因的表达谱。 Ly6C(low) IMs 表现出抗炎和组织保护表型；相比之下，Ly6C(hi) IMs 表现出促炎、组织损伤的表型。当小鼠长期喂食乙醇时，Ly6C(hi)/Ly6C(low)的比值增加，从而显着加剧肝损伤。此外，在吞噬凋亡肝细胞后，Ly6C(hi) IM 转变为 Ly6C(low) IM。综上所述，慢性乙醇喂养会诱导肝脏 IM 的两个子集的募集，它们在调节肝脏炎症和修复方面发挥不同甚至相反的作用。这些发现不仅可以增加我们对 Macs 在 ALD 发病机制中复杂功能的理解，还可以帮助我们确定治疗这种疾病的新治疗靶点。
Hepatic Macs, consisting of resident KCs and infiltrating monocytes/IMs, are thought to play an important role in the pathogenesis of ALD. Previous work has focused on KCs or studied hepatic Macs as one cell population. The aim of the current study is to distinguish IMs from KCs and to compare their phenotypes and functions. We show here that a 4-week ethanol feeding of C57BL/6J mice causes recruitment of IMs into the liver. KCs and IMs can be distinguished based on their differential expression of F4/80 and CD11b. IMs can be divided further into two subsets based on their differential expression of Ly6C. KCs and two subsets of IMs were separately purified by FACS. The phagocytosis abilities and the expression profiles of genes related to various functions were compared among different populations of hepatic Macs. Ly6C(low) IMs exhibit an anti-inflammatory and tissue-protective phenotype; in contrast, Ly6C(hi) IMs exhibit a proinflammatory, tissue-damaging phenotype. The ratio of Ly6C(hi)/Ly6C(low) increases when mice chronically fed ethanol were binged, which significantly enhanced liver injury. Moreover, upon phagocytosis of apoptotic hepatocytes, Ly6C(hi) IMs switch to Ly6C(low) IMs. Taken together, chronic ethanol feeding induces the recruitment of two subsets of hepatic IMs, which play different or even opposite roles in regulating liver inflammation and repair. These findings may not only increase our understanding of the complex functions of Macs in the pathogenesis of ALD but also help us to identify novel therapeutic targets for the treatment of this disease.