کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10738699 | 1046725 | 2011 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Elevated mitochondrial superoxide disrupts normal T cell development, impairing adaptive immune responses to an influenza challenge
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کلمات کلیدی
dihydrodichlorofluorescein diacetateHBSSRNSDCFH-DANBTIFN-γSOD1SOD2IAVMFISOD3LCKPBSCre/loxP - Cre / loxPO2•− - O2 • -ONOO− - ONOO-ROS - ROSnitroblue tetrazolium - tetrazolium nitroblueAntioxidants - آنتی اکسیدانInfluenza - آنفلوانزا adaptive immunity - ایمنی سازگاریTem - این استinterferon-γ - اینترفرون-γTransgenic - تراریختهtumor necrosis factor-α - تومور نکروز عامل αApoptosis - خزان یاختهایdihydroethidium - دی هیدروتیدیمFree radicals - رادیکال آزادHydroxyl radical - رادیکال هیدروکسیلDevelopmental biology - زیست شناسی تکاملیSuperoxide - سوپر اکسیدextracellular superoxide dismutase - سوپر اکسید دیسموتاز خارج سلولیmanganese superoxide dismutase - سوپر اکسید دیسموتاز منگنزTNF-α - فاکتور نکروز توموری آلفاPhosphate-buffered saline - محلول نمک فسفات با خاصیت بافریcopper/zinc superoxide dismutase - مس / روی سوپراکسید دیسموتازMouse - موشmean fluorescence intensity - میانگین شدت فلورسانسTransmission electron microscopy - میکروسکوپ الکترونی عبوریDHE - وInfluenza A virus - ویروس آنفولانزا A Peroxynitrite - پروکسی نیتریتImmunodeficiency - کمبود ایمنیreactive nitrogen species - گونه های واکنش پذیر نیتروژنReactive oxygen species - گونههای فعال اکسیژن•OH - • OH
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Reactive oxygen species (ROS) are critical in a broad spectrum of cellular processes including signaling, tumor progression, and innate immunity. The essential nature of ROS signaling in the immune systems of Drosophila and zebrafish has been demonstrated; however, the role of ROS, if any, in mammalian adaptive immune system development and function remains unknown. This work provides the first clear demonstration that thymus-specific elevation of mitochondrial superoxide (O2
- â) disrupts normal T cell development and impairs the function of the mammalian adaptive immune system. To assess the effect of elevated mitochondrial superoxide in the developing thymus, we used a T-cell-specific knockout of manganese superoxide dismutase (i.e., SOD2) and have thus established a murine model to examine the role of mitochondrial superoxide in T cell development. Conditional loss of SOD2 led to increased superoxide, apoptosis, and developmental defects in the T cell population, resulting in immunodeficiency and susceptibility to the influenza A virus H1N1. This phenotype was rescued with mitochondrially targeted superoxide-scavenging drugs. These findings demonstrate that loss of regulated levels of mitochondrial superoxide lead to aberrant T cell development and function, and further suggest that manipulations of mitochondrial superoxide levels may significantly alter clinical outcomes resulting from viral infection.
- â) disrupts normal T cell development and impairs the function of the mammalian adaptive immune system. To assess the effect of elevated mitochondrial superoxide in the developing thymus, we used a T-cell-specific knockout of manganese superoxide dismutase (i.e., SOD2) and have thus established a murine model to examine the role of mitochondrial superoxide in T cell development. Conditional loss of SOD2 led to increased superoxide, apoptosis, and developmental defects in the T cell population, resulting in immunodeficiency and susceptibility to the influenza A virus H1N1. This phenotype was rescued with mitochondrially targeted superoxide-scavenging drugs. These findings demonstrate that loss of regulated levels of mitochondrial superoxide lead to aberrant T cell development and function, and further suggest that manipulations of mitochondrial superoxide levels may significantly alter clinical outcomes resulting from viral infection.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Free Radical Biology and Medicine - Volume 50, Issue 3, 1 February 2011, Pages 448-458
Journal: Free Radical Biology and Medicine - Volume 50, Issue 3, 1 February 2011, Pages 448-458
نویسندگان
Adam J. Case, Jodi L. McGill, Lorraine T. Tygrett, Takuji Shirasawa, Douglas R. Spitz, Thomas J. Waldschmidt, Kevin L. Legge, Frederick E. Domann,