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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Nitric oxide inhibits exocytosis of cytolytic granules from lymphokine-activated killer cells
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Nitric oxide inhibits exocytosis of cytolytic granules from lymphokine-activated killer cells

机译:一氧化氮抑制淋巴因子激活的杀伤细胞的溶细胞颗粒的胞吐作用

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摘要

NO inhibits cytotoxic T lymphocyte killing of target cells, although the precise mechanism is unknown. We hypothesized that NO decreases exocytosis of cytotoxic granules from activated lymphocytes. We now show that NO inhibits lymphokine-activated killer cell killing of K562 target cells. Exogenous and endogenous NO decreases the release of granzyme 13, granzyme A, and perforin: all contents of cytotoxic granules. NO inhibits the signal transduction cascade initiated by cross-linking of the T cell receptor that leads to granule exocytosis. In particular, we found that No decreases the expression of Ras, a critical signaling component within the exocytic pathway. Ectopic expression of Ras prevents NO inhibition of exocytosis. Our data suggest that Ras mediates NO inhibition of lymphocyte cytotoxicity and emphasize that alterations in the cellular redox state may regulate the exocytic signaling pathway.
机译:NO抑制靶细胞的细胞毒性T淋巴细胞杀伤,尽管其确切机制尚不清楚。我们假设NO减少了活化淋巴细胞的细胞毒性颗粒的胞吐作用。现在我们显示,NO抑制K562目标细胞的淋巴因子激活的杀伤细胞杀伤。外源性和内源性NO可降低颗粒酶13,颗粒酶A和穿孔素的释放:所有细胞毒性颗粒的含量。 NO抑制了由T细胞受体的交联引发的信号转导级联反应,从而导致颗粒胞吐作用。特别是,我们发现No会降低Ras的表达,Ras是胞外途径中的关键信号成分。 Ras的异位表达可防止NO抑制胞吐作用。我们的数据表明Ras介导NO抑制淋巴细胞的细胞毒性,并强调细胞氧化还原状态的改变可能会调节胞外信号通路。

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