The CD16-CD56bright NK cell subset is resistant to reactive oxygen species produced by activated Granulocytes and has higher antioxidative capacity than the CD16+CD56dim subset
The CD16-CD56bright NK cell subset is resistant to reactive oxygen species produced by activated Granulocytes and has higher antioxidative capacity than the CD16+CD56dim subset
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DOI：
10.4049/jimmunol.179.7.4513
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发表时间：
2007-10-01
影响因子：
4.4
通讯作者：
Kiessling, Rolf
中科院分区：
文献类型：
--
作者：
Harlin, Helena;Hanson, Mikael;Kiessling, Rolf
人NK细胞可分为CD56(暗)和CD56(亮)两个亚群。这两种类型的NK细胞对不同类型的刺激有不同的反应，其中CD56(Dim)NK细胞具有直接的细胞毒作用，而CD56(明亮)NK细胞主要具有免疫调节功能。我们发现CD16(+)CD56(Dim)NK亚群对活化的粒细胞诱导的细胞死亡具有敏感性。我们确认过氧化氢(H_2O_2)是粒细胞对CD56(DIM)NK细胞的细胞毒作用的主要效应分子，因为在过氧化氢清除剂过氧化氢酶的存在下，粒细胞杀伤CD56(DIM)NK细胞的能力被完全消除。当NK细胞暴露于H_2O_2时，CD56(Dim)细胞表现出快速的线粒体去极化和激活NKRs的下调，最终导致细胞死亡，而CD56(Bright)细胞未受影响。CD56(DIM)和CD56(Bright)NK细胞对过氧化氢敏感性的差异反映在细胞内氧化水平的差异上，而CD56(Bright)NK细胞的裂解产物具有更强的阻断过氧化氢介导的氧化的能力。我们的数据可能解释了CD56(明亮的)NK细胞优先聚集在富含活性氧物种的环境中，例如在慢性炎症部位和肿瘤中。
Human NK cells can be divided into CD56(dim) and CD56(bright) subsets. These two types of NK cells respond to different types of stimuli, with CD56(dim) NK cells having direct cytotoxic ability and CD56(bright) NK cells having mainly an immunoregulatory function. We show that the CD16(+)CD56(dim) NK subset is characterized by sensitivity to cell death induced by activated granulocytes. We identified hydrogen peroxide (H2O2) as the major effector molecule responsible for the cytotoxic effect of granulocytes on CD56(dim) NK cells, because the ability of granulocytes to kill CD56(dim) NK cells was completely abrogated in the presence of the hydrogen peroxide scavenger catalase. When exposing NK cells to H2O2, CD56(dim) cells showed rapid mitochondrial depolarization and down-regulation of activating NKRs, eventually resulting in cell death, whereas CD56(bright) cells remained unaffected. The difference in sensitivity to H2O2 was mirrored by a difference in intracellular oxidation levels between CD56(dim) and CD56(bright) NK cells, and cell lysates from the latter subset possessed a greater ability to block H2O2-mediated oxidation. Our data may explain the preferential accumulation of CD56(bright) NK cells often seen in environments rich in reactive oxygen species, such as at sites of chronic inflammation and in tumors.