Longoni D, Piemonti L, Bernasconi S, Mantovani A, Allavena P
Department of Immunology and Cell Biology, Mario Negri Institute, Milan, Italy.
Int J Clin Lab Res. 1998;28(3):162-9. doi: 10.1007/s005990050037.
Human monocyte-derived dendritic cells were differentiated in vitro for 7 days with granulocyte macrophage-colony stimulating factor and interleukin-13. These cultured dendritic cells are at an immature stage of differentiation and exhert high endocytic activity via surface mannose receptor and via fluid-phase macropinocytosis. We have investigated the modulation of endocytosis by interleukin-10 in these cells. When added during the last 24 h of the 7-day culture, interleukin-10 significantly stimulated the uptake of fluorescein-labelled dextran (39 +/- 16% increase, mean +/- SD of 6 experiments), a sugar binding to the mannose receptor. This effect was dose dependent and correlated with the length of exposure to interleukin-10, with a maximal effect (more than seven-fold increase) when the cytokine was added at the beginning of the culture (day 0). The interleukin-10-increased fluorescein-labelled-dextran endocytosis was mostly mediated via the mannose receptor, as unlabelled mannose and specific antimannose receptor monoclonal antibody inhibited most of the uptake. Moreover, interleukin-10-treated cells expressed increased levels (up to four-fold) of mannose receptor. Interleukin-10 also increased, although to a lesser extent, the fluid-phase endocytosis (macropinocytosis) of fluorescein-labelled albumin. Interleukin-10 had the opposite effect on the differentiation and functional activity of monocyte-derived dendritic cells; cells having a very low stimulatory capacity and reduced expression of MHC class II and CD1a after a 7-day exposure. Thus interleukin-10 had a strong immunosuppressive effect on the differentiation and functional activity of monocyte-derived dendritic cells and yet strongly stimulated endocytosis in these cells. We speculate that an increased endocytic activity would eventually result in a decreased availability of antigens in the external milieu, thus contributing to the immunosuppressive and tolerogenic activity of interleukin-10.
人单核细胞来源的树突状细胞在体外使用粒细胞巨噬细胞集落刺激因子和白细胞介素-13分化7天。这些培养的树突状细胞处于分化的未成熟阶段，并通过表面甘露糖受体和液相巨胞饮作用发挥高内吞活性。我们研究了白细胞介素-10对这些细胞内吞作用的调节。在7天培养的最后24小时添加白细胞介素-10时，它显著刺激了荧光素标记葡聚糖的摄取（增加39±16%，6次实验的平均值±标准差），葡聚糖是一种与甘露糖受体结合的糖。这种效应呈剂量依赖性，且与暴露于白细胞介素-10的时间长度相关，当在培养开始时（第0天）添加细胞因子时，有最大效应（增加超过7倍）。白细胞介素-10增加的荧光素标记葡聚糖内吞作用主要通过甘露糖受体介导，因为未标记的甘露糖和特异性抗甘露糖受体单克隆抗体抑制了大部分摄取。此外，白细胞介素-10处理的细胞甘露糖受体表达水平增加（高达4倍）。白细胞介素-10也增加了荧光素标记白蛋白的液相内吞作用（巨胞饮作用），尽管程度较小。白细胞介素-10对单核细胞来源的树突状细胞的分化和功能活性有相反的作用；经过7天暴露后，细胞的刺激能力非常低，MHC II类分子和CD1a的表达降低。因此，白细胞介素-10对单核细胞来源的树突状细胞的分化和功能活性有很强的免疫抑制作用，但却强烈刺激这些细胞的内吞作用。我们推测内吞活性增加最终会导致外部环境中抗原可用性降低，从而有助于白细胞介素-10的免疫抑制和致耐受性活性。
