Neutrophil-mediated tissue injury in alcoholic hepatitis
Neutrophil-mediated tissue injury in alcoholic hepatitis
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DOI：
10.1016/s0741-8329(02)00200-8
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发表时间：
2002-05-01
期刊：
影响因子：
2.3
通讯作者：
Jaeschke, H
中科院分区：
文献类型：
--
作者：
Jaeschke, H
肝实质中出现多形核白细胞（中性粒细胞）是酒精性肝炎的一个显著特征。然而，这些吞噬细胞的病理生理学重要性和酒精性肝炎的潜在损伤机制仍不清楚。本文综述了目前的知识的基本机制，嗜水气单胞菌诱导的肝损伤，因为它出现了一些不同的实验模型的研究。嗜酒精性肝炎介导的肝细胞损伤的一般概念与通过检查从酒精性肝炎患者获得的肝切片所做的许多观察一致。这些包括肝脏中存在外渗的中性粒细胞，实质中中性粒细胞脱粒的证据，以及肝细胞中中性粒细胞化学引诱物如CXC趋化因子的过度形成。凋亡肝细胞和中性粒细胞之间的共定位和强定量相关性可能表明酒精性肝炎期间中性粒细胞的凋亡诱导的迁移，类似于先前在实验模型中证明的事件，此外，循环中性粒细胞被激活以形成活性氧和炎性介质。然而，缺乏酒精性肝炎中酒精性肝炎引起损伤的明确证据。不幸的是，大多数酒精性肝病的实验模型没有显著的嗜酸性浸润。因此，未来研究的一个高度优先事项必须是开发一个实验模型，逼真地模拟人类酒精性肝炎的中性粒细胞成分。这将使研究人员能够测试中性粒细胞在酒精性肝炎期间对细胞损伤很重要的概念，并确定潜在的治疗干预策略。(C)2002年爱思唯尔科技有限公司All rights reserved.
The presence of polymorphonuclear leukocytes (neutrophils) in liver parenchyma is a prominent feature of alcoholic hepatitis. However, the pathophysiological importance of these phagocytes and potential injury mechanisms in alcoholic hepatitis remain unclear. This review summarizes the current knowledge on basic mechanisms of neutrophil-induced liver injury as it emerged from studying a number of different experimental models. This general concept of neutrophil-mediated liver cell injury agrees with many observations made by examining liver sections obtained from patients with alcoholic hepatitis. These include the presence of extravasated neutrophils in the liver, evidence for degranulation of neutrophils in the parenchyma, and excessive formation of neutrophil chemoattractants such as CXC chemokines in liver cells, Colocalization and a strong quantitative correlation between apoptotic hepatocytes and neutrophils could indicate apoptosis-induced transmigration of neutrophils during alcoholic hepatitis, similar to events previously demonstrated in experimental models, Furthermore, circulating neutrophils are primed for reactive oxygen species and inflammatory mediator formation. However, clear evidence for a neutrophil-induced injury in alcoholic hepatitis is missing. Unfortunately, most experimental models of alcoholic liver disease do not have a prominent neutrophilic infiltrate. Therefore, a high priority of future research has to be to develop an experimental model that realistically mimics the neutrophil component of alcoholic hepatitis in human beings. This would allow investigators to test the concept that neutrophils are important for cell injury during alcoholic hepatitis and to identify potential therapeutic intervention strategies. (C) 2002 Elsevier Science Inc. All rights reserved.