Peripheral blood monocytes are responsible for gammadelta T cell activation induced by zoledronic acid through accumulation of IPP/DMAPP.
Peripheral blood monocytes are responsible for gammadelta T cell activation induced by zoledronic acid through accumulation of IPP/DMAPP.
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DOI：
10.1111/j.1365-2141.2008.07435.x
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发表时间：
2009-01
影响因子：
6.5
通讯作者：
Thompson K
中科院分区：
文献类型：
--
作者：
Roelofs AJ;Jauhiainen M;Mönkkönen H;Rogers MJ;Mönkkönen J;Thompson K
含氮二膦酸盐通过抑制法尼基焦磷酸合酶和异戊烯基二磷酸（IPP）和二甲基烯丙基二磷酸（DMAPP）的细胞内积累间接激活Vγ9Vδ2 T细胞，但通过IPP/DMAPP积累负责Vγ9Vδ2 T细胞激活的细胞尚不清楚。人外周血单核细胞（PBMC）与唑来膦酸的治疗相关浓度诱导的积累IPP/DMAPP选择性单核细胞，这与这些细胞的有效药物摄取。此外，唑来膦酸脉冲的单核细胞以细胞接触依赖性方式触发γδ T细胞的活化。这些观察结果将单核细胞鉴定为直接受负责Vγ 9VS 2 T细胞活化的双膦酸盐影响的细胞类型。
Nitrogen-containing bisphosphonates indirectly activate Vγ9Vδ2 T cells through inhibition of farnesyl pyrophosphate synthase and intracellular accumulation of isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP), but the cells responsible for Vγ9Vδ2 T cell activation through IPP/DMAPP accumulation are unknown. Treatment of human peripheral blood mononuclear cells (PBMCs) with a pharmacologically relevant concentration of zoledronic acid induced accumulation of IPP/DMAPP selectively in monocytes, which correlated with efficient drug uptake by these cells. Furthermore, zoledronic acid-pulsed monocytes triggered activation of γδ T cells in a cell contact-dependent manner. These observations identify monocytes as the cell type directly affected by bisphosphonates responsible for Vγ9Vδ2 T cell activation.
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影响因子：
20.3
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