Re-organization of mitochondria at the NK cell immune synapse
Re-organization of mitochondria at the NK cell immune synapse
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DOI：
10.1016/j.imlet.2008.10.008
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发表时间：
2009-01-29
影响因子：
4.4
通讯作者：
Javier Sanchez-Garcia, F.
中科院分区：
文献类型：
--
作者：
Abarca-Rojano, Edgar;Muniz-Hernandez, Sae;Javier Sanchez-Garcia, F.
作为先天免疫反应的一部分，NK细胞在激活后数小时内摧毁受感染、转化或应激的细胞。相比之下，在增殖和分化为效应细胞的过程中，CD4(+)T淋巴细胞需要持续增加其代谢，以应对细胞成分的生物发生。最近，线粒体参与了T淋巴细胞免疫突触功能，但对线粒体在NK细胞与肿瘤细胞相互作用中的作用知之甚少。在这里，我们分析了NK细胞线粒体膜电位(Delta psi(M))作为线粒体能量状态和细胞内稳态的指标。当NK细胞与K562肿瘤细胞接触时，NK细胞经历Delta psi(M)去极化，表明其代谢能量迅速消耗。此外，药物对ATP合成的抑制下调了NK细胞的细胞毒活性。共聚焦和电子显微镜分析显示，NK细胞线粒体向与K562肿瘤细胞(NK细胞免疫突触)相互作用的部位重组，这可能是一种补偿局部能量消耗的方式。有趣的是，在NK细胞被抗NKGD2抗体而不是抗KIR2DL1抗体刺激后，线粒体也发生了重组，这表明NK细胞受体触发的激活而不是抑制细胞信号转导参与了NK细胞线粒体的动力学。(C)2008爱思唯尔B.V.保留所有权利。
As part of the innate immune response NK cells destroy infected, transformed, or otherwise stressed cells within hours of activation. In contrast, CD4(+) T lymphocytes require a sustained increase in their metabolism in order to cope with the biogenesis of cell components, in a process of proliferation and differentiation into effector cells.Recently, mitochondria have been implied in T lymphocyte immune synapse function but little is known on the role of mitochondria in the NK cell interaction with tumour cells. Here we analysed NK cells mitochondrial membrane potential (Delta psi(m)) as an indicator of mitochondrial energy status and cellular homeostasis. Upon contact with K562 tumour cells, NK cells undergo Delta psi(m) depolarization, indicating a rapid consumption of their metabolic energy. Furthermore, pharmacological inhibition of ATP synthesis down-regulates NK cell cytotoxic activity.Confocal- and electron-microscopy analyses showed re-organization of NK cells mitochondria towards the site of interaction with K562 tumour cell (NK cell immune synapse), perhaps as a way to compensate for local energy consumption. Interestingly, mitochondrial re-orgainization also takes place following NK stimulation with anti-NKGD2 antibodies but not with anti-KIR2DL1 antibodies, suggesting that activating rather than inhibiting cell signalling, triggered by NK cell receptors, is involved in NK cell mitochondria dynamics. (C) 2008 Elsevier B.V. All rights reserved.