Milk-derived GM3 and GD3 differentially inhibit dendritic cell maturation and effector functionalities
Milk-derived GM3 and GD3 differentially inhibit dendritic cell maturation and effector functionalities
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DOI：
10.1111/j.1365-3083.2005.01566.x
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发表时间：
2005-06-01
影响因子：
3.7
通讯作者：
Frokiær, H
中科院分区：
文献类型：
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作者：
Bronnum, H;Seested, T;Frokiær, H
神经节苷脂是一种复杂的鞘糖脂，对多种细胞类型发挥免疫调节作用。神经节苷脂GD（3）和GM（3）是母乳中主要的神经节苷脂，但在泌乳早期，GD（3）含量降低，而GM（3）含量升高。母乳中神经节苷脂的生物学价值尚未阐明，但当摄入牛奶时，饮食神经节苷脂可能在概念上影响免疫细胞，如树突状细胞（DC）。在这项研究中，我们解决了GD（3）和GM（3）对DC效应器功能的体外作用。在脂多糖诱导成熟之前用GD（3）处理骨髓来源的DC降低了白细胞介素-6（IL-6）、IL-10、IL-12和肿瘤坏死因子-α的产生，并降低了混合白细胞反应（MLR）中的同种异体反应性。相反，GM仅显著抑制IL-10和IL-12的产生（3，），并且MLR中DC激活CD 4（+）细胞的能力不受GM影响（3）。然而，两种神经节苷脂抑制DC上的CD 40、CD 80、CD 86和主要组织相容性复合物II类的表达。由于GD（3）总体上比GM（3）更能抑制DC功能，因此母乳中神经节苷脂部分的免疫调节作用可能在乳汁中含有最多GD（3）的泌乳期开始时更为突出。
Gangliosides are complex glycosphingolipids, which exert immune-modulating effects on various cell types. Ganglioside GD(3) and GM(3) are the predominant gangliosides of human breast milk but during the early phase of lactation, the content of GD(3) decreases while GM(3) increases. The biological value of gangliosides in breast milk has yet to be elucidated but when milk is ingested, dietary gangliosides might conceptually affect immune cells, such as dendritic cells (DCs). In this study, we address the in vitro effect of GD(3) and GM(3) on DC effector functionalities. Treatment of bone marrow-derived DCs with GD(3) before lipopolysaccharide-induced maturation decreased the production of interleukin-6 (IL-6), IL-10, IL-12 and tumor necrosis factor-alpha as well as reduced the alloreactivity in mixed leucocyte reaction (MLR). In contrast, only IL-10 and IL-12 productions were significantly inhibited by GM(3,) and the potency of DCs to activate CD4(+) cells in MLR was unaffected by GM(3). However, both gangliosides suppressed expression of CD40, CD80, CD86 and major histocompatibility complex class II on DCs. Because GD(3) overall inhibits DC functionalities more than GM(3), the immune modulating effect of the ganglioside fraction of breast milk might be more prominent in the commencement of lactation during which the milk contains the most GD(3).