Subcompartments of the macrophage recycling endosome direct the differential secretion of IL-6 and TNFalpha.
Subcompartments of the macrophage recycling endosome direct the differential secretion of IL-6 and TNFalpha.
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DOI：
10.1083/jcb.200612131
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发表时间：
2007-07-02
期刊：
影响因子：
--
通讯作者：
Stow JL
中科院分区：
文献类型：
--
作者：
Manderson AP;Kay JG;Hammond LA;Brown DL;Stow JL
活化的巨噬细胞分泌一系列促炎性细胞因子，包括肿瘤坏死因子-α（TNFα）和白细胞介素6（IL-6），它们在炎症中暂时分泌并发挥顺序作用。我们先前已经表征了膜结合的TNFα的细胞内运输及其在吞噬杯部位递送至细胞表面用于分泌的方面（Murray，R.Z.，J.G.好吧丹吉Sangermani和J.L. Stow. 2005.科学310：1492-1495）。运输途径和表面交付的IL-6，可溶性细胞因子，在这里研究使用的方法，如活细胞成像的荧光标记的IL-6和免疫电子显微镜。新合成的IL-6在高尔基复合体中积累，并作为唯一标记的货物或与TNFα一起存在于管泡载体中，利用特异性可溶性NSF附着蛋白受体（SNARE）蛋白与再循环内体融合。在再循环内体中，我们证明了货物蛋白的区室化，其中IL-6与TNFα和表面再循环转铁蛋白动态分离。此后，这些细胞因子被独立分泌，TNFα被递送至吞噬杯，而IL-6不被递送至吞噬杯。因此，再循环内体在炎症期间协调细胞因子的差异分泌中具有核心作用。
Activated macrophages secrete an array of proinflammatory cytokines, including tumor necrosis factor-α (TNFα) and interleukin 6 (IL-6), that are temporally secreted for sequential roles in inflammation. We have previously characterized aspects of the intracellular trafficking of membrane-bound TNFα and its delivery to the cell surface at the site of phagocytic cups for secretion (Murray, R.Z., J.G. Kay, D.G. Sangermani, and J.L. Stow. 2005. Science. 310:1492–1495). The trafficking pathway and surface delivery of IL-6, a soluble cytokine, were studied here using approaches such as live cell imaging of fluorescently tagged IL-6 and immunoelectron microscopy. Newly synthesized IL-6 accumulates in the Golgi complex and exits in tubulovesicular carriers either as the sole labeled cargo or together with TNFα, utilizing specific soluble NSF attachment protein receptor (SNARE) proteins to fuse with the recycling endosome. Within recycling endosomes, we demonstrate the compartmentalization of cargo proteins, wherein IL-6 is dynamically segregated from TNFα and from surface recycling transferrin. Thereafter, these cytokines are independently secreted, with TNFα delivered to phagocytic cups but not IL-6. Therefore, the recycling endosome has a central role in orchestrating the differential secretion of cytokines during inflammation.
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影响因子：
3.1
作者：
BARTON, BE;JACKSON, JV
通讯作者：
JACKSON, JV
影响因子：
4.5
作者：
Brown, DL;Heimann, K;Gleeson, PA
通讯作者：
Gleeson, PA
DOI：
10.1083/jcb.200408165
发表时间：
2004-11-08
期刊：
The Journal of cell biology
影响因子：
--
作者：
Ang AL;Taguchi T;Francis S;Fölsch H;Murrells LJ;Pypaert M;Warren G;Mellman I
通讯作者：
Mellman I
DOI：
10.1073/pnas.97.2.680
发表时间：
2000-01-18
影响因子：
11.1
作者：
Cox, D;Lee, DJ;Greenberg, S
通讯作者：
Greenberg, S
影响因子：
3.3
作者：
Casanova, JE;Wang, XY;Goldenring, JR
通讯作者：
Goldenring, JR