循環するミトコンドリアのDAMPは,損傷に対する炎症反応を引き起こす
Qin Zhang1, Mustafa Raoof, Yu Chen
1Department of Surgery, Division of Trauma, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA.
Nature
|March 6, 2010
まとめ
傷害により,免疫細胞を活性化させるミトコンドリア損傷に関連した分子パターン (DAMP) が放出され,敗血症を模倣する. これらのミトコンドリアのDAMPは,臓器の損傷に寄与し,トラウマを全身の炎症と結びつける.
科学分野:
- 免疫学 免疫学とは
- 細胞生物学 細胞生物学
- トラウマ研究 トラウマ・リサーチ
背景:
- 損傷後の全身性炎症反応症候群 (SIRS) は,敗血症に似ている.
- 生まれつきの免疫は,病原体関連分子パターン (PAMP) と損傷関連分子パターン (DAMP) によって活性化されます.
- 細菌起源のミトコンドリアは,細胞損傷時に免疫活性化分子を放出することがあります.
研究 の 目的:
- 怪我によってミトコンドリアのDAMP (MTD) が放出されるかどうかを調査する.
- 循環中のMTDsの免疫的影響を決定する.
- トラウマとSIRSを結びつけるMTDの役割を調査する.
主な方法:
- 怪我後に放出された循環因子の分析.
- MTD (ホルミルペプチド,ミトコンドリアDNA) で刺激されたヒトポリモルフォ核中性子 (PMN) を用いた活性化アッセイ.
- カルシウム流量,MAPキナーゼのリン酸化,移動,および脱粒化を含むPMN応答の評価 in vitroおよびin vivo.
主要な成果:
- 傷害は,ホルミルペプチドやミトコンドリアDNAを含むMTDを循環に放出します.
- MTDは,ホルミルペプチド受容体-1とToll型受容体9を介してPMNを活性化します.
- MTDはPMNの活性化,移動,脱粒化を促進し,臓器損傷につながる.
結論:
- 細胞損傷によって放出されたミトコンドリアのDAMPは,セプシスに似た経路を通じて先天的免疫を活性化させます.
- MTDは内生的な危険信号として作用し,トラウマをセプシスのような炎症状態と結びつける.
- ミトコンドリアは,傷害後の炎症を悪化させる"内部敵"の重要な源である.
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