循环中的线粒体DAMP会导致对损伤的炎症反应
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
概括
损伤释放线粒体损伤相关的分子模式 (DAMPs),激活免疫细胞,模仿败血症. 这些线粒体DAMP有助于器官损伤,并将创伤与全身炎症联系起来.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 创伤研究 创伤研究
背景情况:
- 伤害后的全身炎症反应综合征 (SIRS) 类似于败血症.
- 天生的免疫力是由病原体相关的分子模式 (PAMPs) 和损伤相关的分子模式 (DAMPs) 激活的.
- 具有细菌起源的线粒体在细胞损伤时可能会释放免疫激活分子.
研究的目的:
- 为了调查伤害是否释放线粒体DAMP (MTD).
- 为了确定循环的MTDs的免疫后果.
- 探索MTDs在创伤与SIRS联系中的作用.
主要方法:
- 分析受伤后释放的循环因素.
- 使用人类多态核中性粒细胞 (PMNs) 刺激的MTDs (甲基,线粒体DNA) 进行激活试验.
- 在体外和体内评估PMN反应,包括流量,MAP激酶酸化,迁移和脱粒化.
主要成果:
- 伤害释放MTDs,包括甲基和线粒体DNA,进入循环.
- MTDs通过甲基受体-1和Toll类受体9激活PMN.
- 脑筋疲劳症促进PMN的激活,迁移和脱粒,导致器官损伤.
结论:
- 细胞损伤释放的线粒体DAMP通过类似于败血症的途径激活先天免疫力.
- 脊髓炎症作为内生危险信号,将创伤与败血症类炎症状态联系起来.
- 线粒体代表"内部敌人"的关键来源,这些敌人会在受伤后加剧炎症.
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