Mitochondrial uncoupling protein 2 inhibits mast cell activation and reduces histamine content.
Mitochondrial uncoupling protein 2 inhibits mast cell activation and reduces histamine content.
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DOI：
10.4049/jimmunol.0803422
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发表时间：
2009-11-15
期刊：
影响因子：
--
通讯作者：
Theoharides TC
中科院分区：
文献类型：
--
作者：
Tagen M;Elorza A;Kempuraj D;Boucher W;Kepley CL;Shirihai OS;Theoharides TC
肥大细胞是免疫效应细胞，通过释放介质如组胺、肾上腺素和细胞因子参与过敏和炎症。解偶联蛋白2（UCP 2）是一种线粒体蛋白，可能通过下调活性氧（ROS）的产生来抑制β细胞的胰岛素分泌。我们假设UCP 2也可以调节肥大细胞活化。在这里，我们表明，小鼠骨髓肥大细胞（BMMC）和人类白血病LAD 2肥大细胞表达UCP 2。来自UCP 2 −/−小鼠的BMMC表现出更大的组胺释放，而在过敏和非过敏触发后，LAD 2细胞中UCP 2的过表达减少了组胺释放。Ucp 2 −/− BMMCs也有升高的组胺含量和组氨酸脱羧酶表达。组胺含量减少UCP 2的过度表达或治疗与神经靶向超氧化物歧化酶（SOD）模拟TBAP。此外，Ucp 2 −/− BMMCs还具有更高的IL-6和前列腺素D2（PGD 2）产量，以及ERK磷酸化，这是已知的调节前列腺素合成。皮内给予P物质（SP），一种皮肤肥大细胞的激活剂，并在被动致敏后用DNP-HSA激发，在体内诱导Ucp 2 −/−小鼠皮肤中血管通透性显著增加。我们的研究结果表明，UCP 2可以调节肥大细胞活化。
Mast cells are immune effector cells that are involved in allergies and inflammation through the release of mediators such as histamine, prostaglandins and cytokines. Uncoupling protein 2 (UCP2) is a mitochondrial protein that inhibits insulin secretion from β-cells, possibly through downregulation of reactive oxygen species (ROS) production. We hypothesized that UCP2 could also regulate mast cell activation. Here we show that mouse bone marrow mast cells (BMMCs) and human leukemic LAD2 mast cells express UCP2. BMMCs from Ucp2−/− mice exhibited greater histamine release, whereas overexpression of UCP2 in LAD2 cells reduced histamine release after both allergic and non-allergic triggers. Ucp2−/− BMMCs also had elevated histamine content and histidine decarboxylase expression. Histamine content was reduced by overexpression of UCP2 or treatment with the mitochondrial-targeted superoxide dismutase (SOD) mimetic TBAP. Furthermore, Ucp2−/− BMMCs also had greater production of both IL-6 and prostaglandin D2 (PGD2), as well as ERK phosphorylation, which is known to regulate prostaglandin synthesis. Intradermal administration of substance P (SP), an activator of skin mast cells, and challenge with DNP-HSA after passive sensitization induced significantly greater vascular permeability in the skin of Ucp2−/− mice in vivo. Our results suggest that UCP2 can regulate mast cell activation.
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影响因子：
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作者：
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DOI：
10.1016/s0006-291x(02)00355-8
发表时间：
2002-05-17
影响因子：
3.1
作者：
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