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KAKEN_24591461seika.pdf
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Download
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:252.8 KB
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フェントン反応による好中球細胞外捕捉現象制御機構の解明と難治性血管炎治療への応用
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フェントン ハンノウ ニ ヨル コウチュウキュウ サイボウガイ ホソク ゲンショウ セイギョ キコウ ノ カイメイ ト ナンチセイ ケッカンエン チリョウ エノ オウヨウ
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Fenton hanno ni yoru kochukyu saibogai hosoku gensho seigyo kiko no kaimei to nanchisei kekkanen chiryo eno oyo
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Regulation of neutrophil extracellular traps via fenton reaction and its application to the treatment of refractory autoimmune vasculitis
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平橋, 淳一
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ヒラハシ, ジュンイチ
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Hirahashi, Junichi
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慶應義塾大学・医学部・講師
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Research team head
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科研費研究者番号 : 70296573
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浦野, 泰照
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ウラノ, ヤステル
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Urano, Yasuteru
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東京大学・大学院医学系研究科生体物理医学専攻医用生体工学講座生体情報学分野・教授
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Research team member
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科研費研究者番号 : 20292956
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大久保, 光修
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オオクボ, コウシュウ
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Okubo, Koshu
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慶應義塾大学・医学部・助教
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Research team member
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科研費研究者番号 : 60749125
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神谷, 真子
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カミヤ, マコ
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Kamiya, Mako
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東京大学・大学院医学系研究科生体物理医学専攻・助教
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Research team member
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科研費研究者番号 : 90596462
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川上, 浩
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カワカミ, ヒロシ
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Kawakami, Hiroshi
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共立女子大学・家政学部・教授
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Research team member
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科研費研究者番号 : 90458860
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2015
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科学研究費補助金研究成果報告書
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2014
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好中球細胞外トラップ(NETs)は外来微生物を捕捉して生体を防御する一方, 自己免疫性疾患や炎症性疾患に深く関与する。我々はNETs構成成分である生体内蛋白ラクトフェリンが自らの陽性荷電により陰性荷電を有するNETsを凝集させてその放出を抑制することを見出した。また, ラクトフェリンが自己免疫性血管炎におけるNETs形成を抑制し病態を改善させることからNETs関連疾患を制御する新たな治療法の候補となるものである。
Neutrophil extracellular traps (NETs) are associated with the development of autoimmune and/or inflammatory diseases. We found that lactoferrin translocates from the cytoplasm to the plasma membrane of neutrophils upon stimulation and strongly suppresses NETs without effects on oxygen radicals generation. Exogenous lactoferrin significantly shrunk the chromatin fibers in the released NETs. The results that lactoferrin removed positive charge failed to inhibit NET formation suggested that charge-charge interaction between lactoferrin and NETs are required in the function. Lactoferrin suppressed development of autoimmune small-vessel vasculitis and NETs release into the circulation. These observations suggest that lactoferrin serves as an intrinsic inhibitor of NETs and subsequent DNA release into the circulation. Taken together, our data indicate that lactoferrin may represent a therapeutic lead for controlling NET release in autoimmune and/or inflammatory diseases.
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研究種目 : 基盤研究(C)
研究期間 : 2012～2014
課題番号 : 24591461
研究分野 : inflammation
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