Kharbanda Kusum K, Chokshi Shilpa, Tikhanovich Irina, Weinman Steven A, New-Aaron Moses, Ganesan Murali, Osna Natalia A
Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE 68105, USA.
Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Biology (Basel). 2023 Feb 6;12(2):255. doi: 10.3390/biology12020255.
Now, much is known regarding the impact of chronic and heavy alcohol consumption on the disruption of physiological liver functions and the induction of structural distortions in the hepatic tissues in alcohol-associated liver disease (ALD). This review deliberates the effects of alcohol on the activity and properties of liver non-parenchymal cells (NPCs), which are either residential or infiltrated into the liver from the general circulation. NPCs play a pivotal role in the regulation of organ inflammation and fibrosis, both in the context of hepatotropic infections and in non-infectious settings. Here, we overview how NPC functions in ALD are regulated by second hits, such as gender and the exposure to bacterial or viral infections. As an example of the virus-mediated trigger of liver injury, we focused on HIV infections potentiated by alcohol exposure, since this combination was only limitedly studied in relation to the role of hepatic stellate cells (HSCs) in the development of liver fibrosis. The review specifically focusses on liver macrophages, HSC, and T-lymphocytes and their regulation of ALD pathogenesis and outcomes. It also illustrates the activation of NPCs by the engulfment of apoptotic bodies, a frequent event observed when hepatocytes are exposed to ethanol metabolites and infections. As an example of such a double-hit-induced apoptotic hepatocyte death, we deliberate on the hepatotoxic accumulation of HIV proteins, which in combination with ethanol metabolites, causes intensive hepatic cell death and pro-fibrotic activation of HSCs engulfing these HIV- and malondialdehyde-expressing apoptotic hepatocytes.
目前，关于长期大量饮酒对酒精性肝病（ALD）中生理肝功能紊乱及肝组织结构畸变的影响，人们已了解很多。本综述探讨了酒精对肝脏非实质细胞（NPCs）活性和特性的影响，这些细胞要么定居于肝脏，要么从体循环渗入肝脏。在嗜肝性感染和非感染性情况下，NPCs在器官炎症和纤维化的调节中都起着关键作用。在此，我们概述了在ALD中NPC功能是如何受到二次打击（如性别以及接触细菌或病毒感染）调节的。作为病毒介导的肝损伤触发因素的一个例子，我们重点关注了酒精暴露增强的HIV感染，因为关于肝星状细胞（HSCs）在肝纤维化发展中的作用，这种组合仅得到了有限的研究。本综述特别关注肝巨噬细胞、HSC和T淋巴细胞及其对ALD发病机制和结局的调节。它还阐述了通过吞噬凋亡小体激活NPCs的过程，这是肝细胞暴露于乙醇代谢产物和感染时常见的现象。作为这种双重打击诱导的凋亡性肝细胞死亡的一个例子，我们讨论了HIV蛋白的肝毒性积累，其与乙醇代谢产物共同作用，导致大量肝细胞死亡以及吞噬这些表达HIV和丙二醛的凋亡肝细胞的HSCs发生促纤维化激活。
