Involvement of the TNF and FasL produced by CD11b Kupffer cells/macrophages in CCl4-induced acute hepatic injury.
Involvement of the TNF and FasL produced by CD11b Kupffer cells/macrophages in CCl4-induced acute hepatic injury.
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CD11b Kupffer 细胞/巨噬细胞产生的 TNF 和 FasL 参与 CCl4 诱导的急性肝损伤。
DOI：
10.1371/journal.pone.0092515
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Seki S
中科院分区：
文献类型：
--
作者：
Sato A;Nakashima H;Nakashima M;Ikarashi M;Nishiyama K;Kinoshita M;Seki S
F4/80+Kupffer细胞分为CD68+Kupffer细胞和CD11b+Kupffer细胞，CD68+Kupffer细胞具有吞噬和ROS产生能力，CD11b+Kupffer细胞具有细胞因子产生能力。四氯化碳(CCl4)诱导的肝损伤是一种众所周知的化学性肝细胞损伤。在本研究中，我们研究了Kupffer细胞/巨噬细胞在CCl4诱导的小鼠肝炎中的免疫作用。肝组织免疫组织化学分析及肝单个核细胞流式细胞仪检测显示，氯膦酸酯脂质体(c-lipo)处理后，梭形F4/80+或CD68+细胞明显减少，椭圆形F4/80+CD11b+细胞明显增多。值得注意的是，c-Lipo预处理可进一步加重CCl_4所致的严重肝损伤。CD11b+Kupffer细胞/巨噬细胞的数量在CCl4注射后24小时显著增加，尤其是在c-Lipo处理的小鼠。CD11b+枯否细胞表达细胞内肿瘤坏死因子和表面Fas配体(FasL)。此外，抗肿瘤坏死因子抗体(降低CD11b+Kupffer细胞FasL表达)、抗FasL抗体预处理或GLD/GLD小鼠均可减轻CCl4所致的肝损伤。CD1d−/−小鼠和细胞耗竭实验表明，NKT细胞和NK细胞不参与肝损伤。过继转移和对原代培养肝细胞的细胞毒试验证实CD11b+Kupffer细胞在CCl4诱导的肝炎中的作用。有趣的是，血清MCP-1水平在c-Lipo6h后迅速升高，并在6h达到峰值，提示c-Lipo吞噬CD68+Kupffer细胞产生的MCP-1可能从外周血和骨髓中募集CD11b+巨噬细胞。CD11b+Kupffer细胞产生的肿瘤坏死因子和FasL在CCl4诱导的急性肝损伤中起关键作用。
We previously reported that F4/80+ Kupffer cells are subclassified into CD68+ Kupffer cells with phagocytic and ROS producing capacity, and CD11b+ Kupffer cells with cytokine-producing capacity. Carbon tetrachloride (CCl4)-induced hepatic injury is a well-known chemical-induced hepatocyte injury. In the present study, we investigated the immunological role of Kupffer cells/macrophages in CCl4-induced hepatitis in mice. The immunohistochemical analysis of the liver and the flow cytometry of the liver mononuclear cells showed that clodronate liposome (c-lipo) treatment greatly decreased the spindle-shaped F4/80+ or CD68+ cells, while the oval-shaped F4/80+ CD11b+ cells increased. Notably, severe hepatic injury induced by CCl4 was further aggravated by c-lipo-pretreatment. The population of CD11b+ Kupffer cells/macrophages dramatically increased 24 hour (h) after CCl4 administration, especially in c-lipo-pretreated mice. The CD11b+ Kupffer cells expressed intracellular TNF and surface Fas-ligand (FasL). Furthermore, anti-TNF Ab pretreatment (which decreased the FasL expression of CD11b+ Kupffer cells), anti-FasL Ab pretreatment or gld/gld mice attenuated the liver injury induced by CCl4. CD1d−/− mouse and cell depletion experiments showed that NKT cells and NK cells were not involved in the hepatic injury. The adoptive transfer and cytotoxic assay against primary cultured hepatocytes confirmed the role of CD11b+ Kupffer cells in CCl4-induced hepatitis. Interestingly, the serum MCP-1 level rapidly increased and peaked at six h after c-lipo pretreatment, suggesting that the MCP-1 produced by c-lipo-phagocytized CD68+ Kupffer cells may recruit CD11b+ macrophages from the periphery and bone marrow. The CD11b+ Kupffer cells producing TNF and FasL thus play a pivotal role in CCl4-induced acute hepatic injury.
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DOI：
10.1159/000157141
发表时间：
1989-03-01
期刊：
PATHOLOGY AND IMMUNOPATHOLOGY RESEARCH
影响因子：
--
作者：
CLAWSON, GA
通讯作者：
CLAWSON, GA
影响因子：
29.4
作者：
Liu, ZX;Govindarajan, S;Kaplowitz, N
通讯作者：
Kaplowitz, N
影响因子：
5
作者：
Liu, Cheng;Tao, Qing;Liu, Ping
通讯作者：
Liu, Ping
DOI：
10.1073/pnas.93.25.14833
发表时间：
1996-12-10
影响因子：
11.1
作者：
Ramprasad, MP;Terpstra, V;Steinberg, D
通讯作者：
Steinberg, D
影响因子：
5.5
作者：
Holt, Michael P.;Cheng, LinLing;Ju, Cynthia
通讯作者：
Ju, Cynthia