Characterization of two F4/80-positive Kupffer cell subsets by their function and phenotype in mice
Characterization of two F4/80-positive Kupffer cell subsets by their function and phenotype in mice
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DOI：
10.1016/j.jhep.2010.04.037
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发表时间：
2010-11-01
影响因子：
25.7
通讯作者：
Seki, Shuhji
中科院分区：
文献类型：
--
作者：
Kinoshita, Manabu;Uchida, Takefumi;Seki, Shuhji
背景与目的：肝枯否细胞是一种异质性巨噬细胞系细胞。我们探讨了这种可能性，通过将小鼠枯否细胞分为亚群，并通过其表型和functions.Methods：肝单核细胞（MNCs）从C57 BL/6小鼠分离，并分析其表型和功能。结果：25%左右的肝单个核细胞为F4/80（+）Kupffer细胞。其中，46%为CD 11b（-）CD 68（+），22%为CD 11b（+）CD 68（-），6%为CD 11b（+）CD 68（+）。脂多糖（LPS）刺激后，CD 68（+）细胞显示出强大的吞噬活性和活性氧（ROS）产生能力，而CD 11b（+）细胞则没有。CD 11b（+）细胞显示出较强的细胞因子（TNF和IL-12）产生能力，这在CD 68（+）细胞中不太突出。LPS或大肠杆菌注射后24 h，CD 11b（+）CD 68（-）和CD 11b（+）CD 68（+）细胞比例增加，而CD 11b（-）CD 68（+）细胞比例下降。CD 11b（+）CD 68（+）细胞的增加似乎来源于CD 11b（+）CD 68（-）亚群。虽然CD 11b（+）细胞在LPS注射后增强了吞噬活性，但它们并没有增加ROS的产生，这表明它们的溶解活性较弱。给小鼠注射氯膦酸盐或GdCl 3可使CD 68（+）细胞减少，但使CD 11b（+）细胞成比例增加，因为CD 68（+）细胞可吞噬这些毒性试剂并发生凋亡。结论：F4/80（+）Kupffer细胞可能存在两个亚群，一个是具有吞噬活性的CD 68（+）亚群，一个是具有产生精氨酸能力的CD 11b（+）亚群。(C)2010年欧洲肝脏研究协会。Elsevier B. V.出版，保留所有权利。
Background & Aims: Liver Kupffer cells have been suggested to be heterogeneous macrophage lineage cells. We explored this possibility by classifying the mouse Kupffer cells into subpopulations and characterizing them by their phenotype and function.Methods: Liver mononuclear cells (MNCs) from C57BL/6 mice were isolated and their phenotypes and functions were analyzed. The effects of clodronate liposomes and gadolinium chloride (GdCl3) on Kupffer cells were also investigated.Results: Approximately 25% of liver MNCs were F4/80(+) Kupffer cells. Of these, 46% were CD11b(-)CD68(+), 22% were CD11b(+)CD68(-), and 6% were CD11b(+)CD68(+). CD68(+) cells showed potent phagocytic activity and reactive oxygen species (ROS) production capacity after lipopolysaccharide (LPS) stimulation, whereas CD11b(+) cells did not. CD11b(+) cells showed a strong capacity for the production of cytokines (TNF and IL-12), which was much less prominent in CD68(+) cells. At 24h after LPS or Escherichia coli injection into mice, the proportions of CD11b(+)CD68(-) and CD11b(+)CD68(+) cells increased but that of CD11b(-)CD68(+) cells decreased. The increase in CD11b(+)CD68(+) cells appeared to be derived from the CD11b(+)CD68(-) subset. Although the CD11b(+) cells augmented phagocytic activity after LPS injection, they did not increase ROS production, suggesting their weak lytic activity. Injection of clodronate or GdCl3 into mice depleted the CD68(+) cells but increased CD11b(+) cells proportionally because CD68(+) cells may phagocytose these toxic reagents and undergo apoptosis. GdCl3-treated mice also consistently increased serum TNF after LPS challenge.Conclusions: Two F4/80(+) Kupffer cell subsets may exist, a CD68(+) subset with phagocytic activity and a CD11b(+) subset with cytokine-producing capacity. (C) 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.