NK-92自然杀伤细胞中钙调神经磷酸酶依赖性溶细胞颗粒胞吐作用。
Calcineurin-dependent lytic granule exocytosis in NK-92 natural killer cells.
作者信息
Pores-Fernando Arun T, Gaur Surabhi, Doyon Michelle Y, Zweifach Adam
机构信息
Department of Molecular and Cell Biology, University of Connecticut at Storrs, 91 North Eagleville Road, CT 06268-3125, USA.
出版信息
Cell Immunol. 2009;254(2):105-9. doi: 10.1016/j.cellimm.2008.07.004. Epub 2008 Aug 30.
Cytotoxic T cells (CTLs) and natural killer cells (NKs) both kill virus-infected cells and tumor cells by releasing the cytoxic contents of their lytic granules. We recently demonstrated a role for calcineurin in lytic granule exocytosis in TALL-104 human leukemic CTLs [M.J. Grybko, J.P. Bartnik, G.A. Wurth, A.T. Pores-Fernando, A. Zweifach, Calcineurin activation is only one calcium-dependent step in cytotoxic T lymphocyte granule exocytosis, J. Biol. Chem. 282 (2007) 18009-18017]. However, whether calcineurin plays a similar role in NK lytic granule release is not known. We tested whether calcineurin is involved in lytic granule exocytosis in human leukemic NK-92 cells using immunosuppressive drugs that block calcineurin function and by overexpressing a constitutively active calcineurin fusion protein. Our results indicate that calcineurin does play a role in lytic granule exocytosis in NK-92 cells, and suggest that, as was the case in TALL-104 cells, there are likely to be multiple calcium-dependent steps.
细胞毒性T细胞（CTLs）和自然杀伤细胞（NKs）均通过释放其溶细胞颗粒中的细胞毒性成分来杀伤病毒感染细胞和肿瘤细胞。我们最近证明了钙调神经磷酸酶在TALL-104人白血病CTLs的溶细胞颗粒胞吐作用中发挥作用[M.J. Grybko，J.P. Bartnik，G.A. Wurth，A.T. Pores-Fernando，A. Zweifach，钙调神经磷酸酶激活只是细胞毒性T淋巴细胞颗粒胞吐作用中一个钙依赖性步骤，《生物化学杂志》282（2007）18009 - 18017]。然而，钙调神经磷酸酶在NK溶细胞颗粒释放中是否发挥类似作用尚不清楚。我们使用阻断钙调神经磷酸酶功能的免疫抑制药物并通过过表达组成型活性钙调神经磷酸酶融合蛋白，来测试钙调神经磷酸酶是否参与人白血病NK-92细胞的溶细胞颗粒胞吐作用。我们的结果表明钙调神经磷酸酶确实在NK-92细胞的溶细胞颗粒胞吐作用中发挥作用，并表明，与TALL-104细胞的情况一样，可能存在多个钙依赖性步骤。
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