Rapamycin inhibits macropinocytosis and mannose receptor-mediated endocytosis by bone marrow-derived dendritic cells
Rapamycin inhibits macropinocytosis and mannose receptor-mediated endocytosis by bone marrow-derived dendritic cells
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DOI：
10.1182/blood.v100.3.1084
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发表时间：
2002-08-01
期刊：
影响因子：
20.3
通讯作者：
Thomson, AW
中科院分区：
文献类型：
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作者：
Hackstein, H;Taner, T;Thomson, AW
树突状细胞 (DC) 是专业的抗原呈递细胞 (APC)，使用 2 条主要途径进行抗原摄取：组成型巨胞饮作用和甘露糖受体介导的内吞作用。有效的内吞作用对于 DC 履行其免疫前哨功能至关重要。我们通过流式细胞术研究了免疫抑制性大环内酯雷帕霉素对异硫氰酸荧光素 (FITC)-白蛋白巨胞饮作用和甘露糖受体介导的小鼠骨髓来源 DC 的 FITC-葡聚糖内吞作用的影响。数据显示，(1) 在生理相关的低浓度 (11 ng/mL) 下，雷帕霉素会损害巨胞饮作用和甘露糖受体介导的内吞作用； (2) 该作用与 DC 成熟无关，并且可以通过 3 色流式细胞术在未成熟的 CD11c(+) 主要组织相容性复合体 (MHC) 11(Io) 类 DC 中特异性证明； (3)内吞作用的抑制与细胞凋亡无关； (4)结构相关分子FK506的摩尔过量抑制雷帕霉素的作用。雷帕霉素对 DC 内吞作用的抑制作用在体内得到证实。据我们所知，这是第一份临床相关免疫抑制剂抑制 DC 内吞作用的报告。 (C) 2002 年，美国血液学会。
Dendritic cells (DCs) are professional antigen-presenting cells (APCs) that use 2 major pathways for antigen uptake: constitutive macropinocytosis and mannose receptor-mediated endocytosis. Efficient endocytosis is critical for DCs to fulfill their sentinel function in immunity. We investigated the influence of the immunosuppressive macrolide rapamycin on macropinocytosis of fluorescein isothiocyanate (FITC)-albumin and mannose receptor-mediated endocytosis of FITC-dextran by murine bone marrow-derived DCs by flow cytometry. The data show that (1) at a low, physiologically relevant concentration (11 ng/mL), rapamycin impairs macropinocytosis and mannose receptor-mediated endocytosis; (2) the effects are independent of DC maturation and can be demonstrated specifically in immature CD11c(+) major histocompatibility complex (MHC) class 11(Io) DCs by 3-color flow cytometry; (3) inhibition of endocytosis is not related to apoptotic cell death; and (4) molar excess of the structurally related molecule FK506 inhibits the actions of rapamycin. The inhibitory effects of rapamycin on DC endocytosis were confirmed in vivo. To our knowledge, this is the first report that a clinically relevant immunosuppressant inhibits DC endocytosis. (C) 2002 by The American Society of Hematology.