Mitochondria distinguish granule-stored from de novo synthesized tumor necrosis factor secretion in human mast cells.
Mitochondria distinguish granule-stored from de novo synthesized tumor necrosis factor secretion in human mast cells.
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DOI：
10.1159/000335178
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发表时间：
2012
影响因子：
2.8
通讯作者：
Theoharides TC
中科院分区：
文献类型：
--
作者：
Zhang B;Weng Z;Sismanopoulos N;Asadi S;Therianou A;Alysandratos KD;Angelidou A;Shirihai O;Theoharides TC
肥大细胞是来源于造血前体的免疫细胞，在组织微环境中成熟。肥大细胞对过敏、免疫和炎症过程至关重要，其中许多过程都涉及肿瘤坏死因子。肥大细胞独特地将TNF储存在其分泌颗粒中。刺激后，肥大细胞迅速（30分钟）通过脱颗粒分泌β -己糖氨基酶（β -hex）和颗粒储存的TNF，但也增加TNF mRNA，并在24小时后释放新合成的TNF。人们对这两种不同途径的调控知之甚少。人LAD2白血病肥大细胞受到P物质（SP）的刺激。采用ELISA和Real-Time PCR检测TNF分泌及基因表达。共聚焦显微镜下观察活细胞线粒体动力学。用耗氧速率测量细胞能量消耗。在这里，我们发现颗粒储存的TNF是预先形成的，SP刺激LAD2肥大细胞分泌的TNF表现出(a)更高的能量消耗，受到线粒体ATP泵阻滞剂寡霉素的抑制，(b)细胞内钙水平的快速增加，以及(c)与脂多糖（LPS）诱导的从头合成的TNF释放相比，从核周围分布到细胞表面的可逆线粒体易位。这种线粒体易位是用过敏触发物（IgE/链亲和素）刺激的人脐带血源性肥大细胞（hCBMCs）证实的。这些发现表明，独特的线粒体功能区分颗粒储存和新合成的TNF释放从人类肥大细胞，从而允许肥大细胞在不同的生物过程中广泛参与。
Mast cells are immune cells derived from hematopoietic precursors that mature in the tissue microenvironment. Mast cells are critical for allergic, immune and inflammatory processes, many of which involve TNF. Mast cells uniquely store TNF in their secretory granules. Upon stimulation, mast cells rapidly (30 min) secrete beta-hexosaminidase (beta-hex) and granule-stored TNF through degranulation, but also increase TNF mRNA and release de novo synthesized TNF 24 hr later. Regulation of these two distinct pathways is poorly understood. human LAD2 leukemic mast cells are stimulated by substance P (SP). TNF secretion and gene expression were measured by ELISA and Real-Time PCR. Live cell mitochondrial dynamics was observed under Confocal Microscopy. Cell energy consumption were measured in term of oxygen consumption rate. Here we show that granule-stored TNF is preformed and its secretion from LAD2 mast cells stimulated by SP exhibits (a) higher energy consumption and is inhibited by the mitochondrial ATP pump blocker oligomycin, (b) rapid increase of intracellular calcium levels, and (c) reversible mitochondrial translocation, from a perinuclear distribution to the cell surface, as compared to de novo synthesized TNF release induced by lipopolysaccharide (LPS). This mitochondrial translocation is confirmed using primary human umbilical cord blood-derived mast cells (hCBMCs) stimulated by an allergic trigger (IgE/streptavidin). These findings indicate that unique mitochondrial functions distinguish granule-stored from newly synthesized TNF release from human mast cells, thus permitting the versatile involvement of mast cells in different biological processes.
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影响因子：
4.8
作者：
Kempuraj, D;Papadopoulou, NG;Theoharides, TC
通讯作者：
Theoharides, TC
影响因子：
64.8
作者：
GORDON, JR;GALLI, SJ
通讯作者：
GALLI, SJ
影响因子：
3.5
作者：
JOHNSON, RG;CARTY, SE;SCARPA, A
通讯作者：
SCARPA, A
影响因子：
2.7
作者：
Kirshenbaum, AS;Akin, C;Metcalfe, DD
通讯作者：
Metcalfe, DD
DOI：
10.1073/pnas.0703126104
发表时间：
2007-09-04
影响因子：
11.1
作者：
Quintana, Ariel;Schwindling, Christian;Hoth, Markus
通讯作者：
Hoth, Markus