Kikuchi Kazuhiro, Yanagawa Yoshiki, Onoé Kazunori
Division of Immunobiology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan.
Microbiol Immunol. 2005;49(6):535-44. doi: 10.1111/j.1348-0421.2005.tb03759.x.
CC chemokine receptor 7 (CCR7) is selectively expressed on mature dendritic cells (DC). The CCR7 ligands, CC chemokine ligand (CCL) 19 and CCL21, facilitate migration of mature DC from the peripheral tissues to regional lymph nodes. We previously demonstrated that CCR7 ligands induced rapid receptor-mediated endocytosis of dextran in mature DC. In the present study, we further examined the effects of CCR7 ligands on endocytosis of other kinds of antigen, mannosilated bovine serum albumin (Mann-BSA), Escherichia coli(E. coli), or ovalbumin-containing immune complex (OVA-IC), by mature DC. We found that CCR7 ligands enhanced the endocytosis of Mann BSA, E. coli, and OVA-IC in mature DC but not in immature DC. The endocytosis of BSA was not enhanced by CCR7 ligands. Furthermore, the phagocytosis of OVA-IC was significantly inhibited by anti-Fcgamma receptor III/II antibody. These results demonstrate that CCR7 ligands enhance only receptor-mediated endocytosis by mature DC. When rapidly phagocytosed E. coli were traced in CCL19-treated mature DC, most of the phagocytosed E. coli did not colocalize with the lysosomal marker: lysosome-associated membrane protein-1 (Lamp-1), whereas most of E. coli taken up relatively slowly by immature DC colocalized with Lamp-1. These results suggest that phagocytosis of antigens by immature and mature DC plays different functional roles.
CC趋化因子受体7(CCR7)在成熟树突状细胞(DC)上选择性表达。CCR7配体,即CC趋化因子配体(CCL)19和CCL21,可促进成熟DC从外周组织迁移至局部淋巴结。我们之前证明CCR7配体可诱导成熟DC中葡聚糖的快速受体介导的内吞作用。在本研究中,我们进一步检测了CCR7配体对成熟DC摄取其他种类抗原(甘露糖化牛血清白蛋白(Mann-BSA)、大肠杆菌(E. coli)或含卵清蛋白的免疫复合物(OVA-IC))的内吞作用的影响。我们发现CCR7配体增强了成熟DC对Mann BSA、大肠杆菌和OVA-IC的内吞作用,但未增强未成熟DC的内吞作用。CCR7配体未增强牛血清白蛋白的内吞作用。此外,抗Fcγ受体III/II抗体可显著抑制OVA-IC的吞噬作用。这些结果表明CCR7配体仅增强成熟DC的受体介导的内吞作用。当在CCL19处理的成熟DC中追踪快速吞噬的大肠杆菌时,大多数吞噬进的大肠杆菌未与溶酶体标志物:溶酶体相关膜蛋白-1(Lamp-1)共定位,而未成熟DC相对缓慢摄取的大多数大肠杆菌与Lamp-1共定位。这些结果表明未成熟和成熟DC对抗原的吞噬作用发挥着不同的功能作用。