Leukocyte activation primes fibrinogen for proteolysis by mitochondrial oxidative stress.
Leukocyte activation primes fibrinogen for proteolysis by mitochondrial oxidative stress.
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DOI：
10.1016/j.redox.2022.102263
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发表时间：
2022-05
期刊：
影响因子：
11.4
通讯作者：
White NJ
中科院分区：
文献类型：
--
作者：
Han CY;Pichon TJ;Wang X;Ringgold KM;St John AE;Stern SA;White NJ
临界疾病会导致纤维蛋白原消耗，高纤维蛋白溶解和凝血病，使出血并增加死亡率。用于管理白细胞相关感染对纤维蛋白原的影响的病理生理机制纤维蛋白原早期被氧化，然后在3个小时的脂多糖（LPS）诱导的无菌炎症后降解。 。 (ROS) from neutrophils, and nitric oxide from lymphocytes and monocytes. Inhibition of mitochondrial superoxide prevented oxidative modification and proteolysis of fibrinogen, whereas inhibition of MPO attenuated only fibrinogen proteolysis. Quenching of both mitochondrial superoxide and MPO-derived ROS prevented coagulopathy better than transexamic酸，这些发现表明中性粒细胞和单核细胞超氧化物的产生可以迅速将氧化物纤维蛋白原作为炎症过程中纤维蛋白原蛋白水解和凝血病的启动步骤。
白细胞诱导的炎症第一氧化物，然后降解纤维蛋白原。
纤维蛋白原通过涉及线粒体和髓过氧化物酶衍生的氧化物胁迫的过程进行蛋白水解。
抗氧化剂抑制氧化应激可以防止纤维蛋白原氧化和降解。
Critical illness leads to rapid fibrinogen consumption, hyperfibrinolysis, and coagulopathy that exacerbates bleeding and increases mortality. Immune cell activation and inflammation are associated with coagulopathy after injury but play an undetermined role. We performed high dimensional immunophenotyping and single-cell imaging flow cytometry to investigate for a pathophysiological mechanism governing the effects of leukocyte-associated inflammation on fibrinogen function. Fibrinogen was oxidized early, followed by its degradation after 3 hours of lipopolysaccharides (LPS)-induced sterile inflammation in a rat model in vivo. Fibrinogen incubated with human leukocytes activated by TNFα was similarly oxidized, and later proteolyzed after 3 hours in vitro. TNFα induced mitochondrial superoxide generation from neutrophils and monocytes, myeloperoxidase (MPO)-derived reactive oxygen species (ROS) from neutrophils, and nitric oxide from lymphocytes and monocytes. Inhibition of mitochondrial superoxide prevented oxidative modification and proteolysis of fibrinogen, whereas inhibition of MPO attenuated only fibrinogen proteolysis. Quenching of both mitochondrial superoxide and MPO-derived ROS prevented coagulopathy better than tranexamic acid. Collectively, these findings indicate that neutrophil and monocyte mitochondrial superoxide generation can rapidly oxidize fibrinogen as a priming step for fibrinogen proteolysis and coagulopathy during inflammation. Leukocyte-induced inflammation first oxidizes, then degrades fibrinogen. Fibrinogen is primed for proteolysis by a process that involves mitochondrial and myeloperoxidase-derived oxidative stress. Inhibition of oxidative stress by antioxidants can prevent both fibrinogen oxidation and degradation.
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影响因子：
4.6
作者：
Lau WH;White NJ;Yeo TW;Gruen RL;Pervushin K
通讯作者：
Pervushin K
影响因子：
39.3
作者：
Liu T;Zhang L;Joo D;Sun SC
通讯作者：
Sun SC
DOI：
10.1097/ta.0b013e318169cd3c
发表时间：
2008-05-01
影响因子：
--
作者：
Brohi, Karim;Cohen, Mitchell J.;Pittet, Jean-Francois
通讯作者：
Pittet, Jean-Francois
影响因子：
14
作者：
Lamm RJ;Lim EB;Weigandt KM;Pozzo LD;White NJ;Pun SH
通讯作者：
Pun SH
影响因子：
64.8
作者：
DOOLITTLE, RF;WATT, KWK;RILEY, M
通讯作者：
RILEY, M