Circulating mitochondrial DAMPs cause inflammatory responses to injury.
Circulating mitochondrial DAMPs cause inflammatory responses to injury.
复制标题
循环线粒体 DAMP 会引起对损伤的炎症反应。
作者：
损伤引起的全身性炎症反应综合征（SIRS）在临床上很像败血症。微生物病原相关分子模式（PAMPs）通过模式识别受体激活先天免疫细胞。同样，细胞损伤可以释放内源性损伤相关分子模式（DAMPs），激活先天免疫。线粒体是进化的内共生体，来源于细菌，因此可能具有细菌的分子基序。我们在这里表明，损伤释放线粒体DAMPs （MTD）进入循环，具有重要的功能免疫后果。MTD包括甲酰基肽和线粒体DNA。它们分别通过甲酰基肽受体1和TLR9激活人中性粒细胞（PMN）。MTD促进PMN Ca2+通量和MAP激酶的磷酸化，从而导致PMN在体内和体外的迁移和脱粒。循环MTD可引起中性粒细胞介导的器官损伤。创伤引起的细胞破坏释放线粒体DAMPs，其进化上保守的相似性与细菌PAMPs进入循环。然后，它们可以通过相同的先天免疫途径发出信号，产生类似败血症的状态。细胞损伤释放这种线粒体“内部敌人”是创伤、炎症和SIRS之间的关键联系。
Injury causes a systemic inflammatory response syndrome (SIRS) clinically much like sepsis. Microbial pathogen-associated molecular patterns (PAMPs) activate innate immunocytes through pattern recognition receptors. Similarly, cellular injury can release endogenous damage-associated molecular patterns (DAMPs) that activate innate immunity. Mitochondria are evolutionary endosymbionts that were derived from bacteria and so might bear bacterial molecular motifs. We show here that injury releases mitochondrial DAMPs (MTD) into the circulation with functionally important immune consequences. MTD include formyl peptides and mitochondrial DNA. These activate human neutrophils (PMN) through formyl peptide receptor-1 and TLR9 respectively. MTD promote PMN Ca2+ flux and phosphorylation of MAP kinases, thus leading to PMN migration and degranulation in vitro and in vivo. Circulating MTD can elicit neutrophil-mediated organ injury. Cellular disruption by trauma releases mitochondrial DAMPs with evolutionarily conserved similarities to bacterial PAMPs into the circulation. These can then signal through identical innate immune pathways to create a sepsis-like state. The release of such mitochondrial ‘enemies within’ by cellular injury is a key link between trauma, inflammation and SIRS.
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DOI：
10.1097/00005373-200004000-00003
发表时间：
2000-04-01
影响因子：
--
作者：
Hauser, CJ;Fekete, Z;Deitch, EA
通讯作者：
Deitch, EA
DOI：
10.1097/00005373-197403000-00001
发表时间：
1974-01-01
影响因子：
--
作者：
BAKER, SP;ONEILL, B;LONG, WB
通讯作者：
LONG, WB
影响因子：
8.8
作者：
Abraham, E
通讯作者：
Abraham, E
影响因子：
5.6
作者：
MARCKER, K;SANGER, F
通讯作者：
SANGER, F
影响因子：
20.3
作者：
Hayashi, F;Means, TK;Luster, AD
通讯作者：
Luster, AD