Involvement of natural killer cells in PolyI:C-induced liver injury
Involvement of natural killer cells in PolyI:C-induced liver injury
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DOI：
10.1016/j.jhep.2004.08.021
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发表时间：
2004-12-01
影响因子：
25.7
通讯作者：
Tian, ZG
中科院分区：
文献类型：
--
作者：
Dong, ZJ;Wei, HM;Tian, ZG
背景/目的：T细胞、自然杀伤T细胞（NKT）和巨噬细胞在自身免疫性肝炎中的作用已被充分证实。然而，自然杀伤（NK）细胞在肝损伤中的作用仍不清楚。在这里，我们研究了聚肌胞苷酸（PolyI：C）激活的NK细胞对肝损伤的影响。方法：小鼠腹腔注射PolyI：C，剂量为20 μ g/g体重。用流式细胞术分析肝脏中NK细胞的百分比和绝对数。结果：PolyI：C注射后，肝脏内NK细胞聚集并活化，肝脏内NK细胞数量明显增加，肝脏内NK细胞数量明显减少。同时，还观察到血清ALT/AST轻度升高，肝脏轻度炎症和局灶性坏死。NK细胞的耗竭显著减弱PolyI：C诱导的肝损伤。枯否细胞产生的内源性白细胞介素-12的中和消除了肝脏中NK细胞的积累和随后的肝损伤。结论：PolyI：C优先募集和激活肝脏NK细胞，可能是轻度肝炎的重要机制。(C)2004年欧洲肝脏研究协会。Elsevier B. V.出版，保留所有权利。
Background/Aims: The roles of T cells, natural killer T cells (NKT) and macrophages in autoimmune hepatitis have been well documented. However, the roles of natural killer (NK) cells in liver injury remain obscure. Here we examined the effect of Polyinosinic: polycytidylic acid (PolyI:C)-activated NK cells on liver injury.Methods: Mice were intraperitoneally injected with PolyI:C at a dose of 20 mug/g body wt. The percentage and absolute number of NK cells in the liver were analyzed with flow cytometry. Serum alanine transaminase (ALT) and aspartate aminotransferase (AST) assay and H-E staining were used to evaluate the liver injury.Results: Following PolyI:C injection, NK cells accumulation and activation occurred in the liver. Meanwhile, slight elevation of ALT/AST in the serum, mild inflammation and focal necrosis in the liver were also observed. Depletion of NK cells markedly attenuated PolyI:C-induced liver injury. Neutralization of endogenous Interleukin-12 produced by Kupffer cells abrogated the accumulation of NK cells in the liver and subsequent liver injury. The liver injury was also alleviated by neutralization of vascular cell adhesive molecule-1.Conclusions: These findings suggest that PolyI:C preferentially recruits and activates hepatic NK cells, which may be responsible for the mild hepatitis. (C) 2004 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.