Complement component 5 promotes lethal thrombosis.
Complement component 5 promotes lethal thrombosis.
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DOI：
10.1038/srep42714
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发表时间：
2017-02-16
影响因子：
4.6
通讯作者：
Imai M
中科院分区：
文献类型：
--
作者：
Mizuno T;Yoshioka K;Mizuno M;Shimizu M;Nagano F;Okuda T;Tsuboi N;Maruyama S;Nagamatsu T;Imai M
细胞外组蛋白促进血小板聚集和血栓形成；随后诱导凝血功能紊乱，导致凝血因子耗竭。补体成分5(C5)与血小板聚集和凝血系统激活有关。到目前为止，肝损伤的病理机制尚不清楚。在这里，我们调查了C5是否促进了与组蛋白诱导的致命性血栓形成相关的肝损伤。C5充足和C5缺乏的小鼠接受单尾静脉注射从小牛胸腺获得的纯化的、未分离的组蛋白(45-75 μg/g)。随后，监测小鼠的存活时间达72 h。根据存活数据，以45 μg/g剂量分析血细胞计数、肝功能、凝血能力以及细胞外组蛋白对血小板聚集和血小板/白细胞聚集的促进作用。与C5缺乏的小鼠相比，C5缺乏的小鼠免受致死性血栓形成的保护，并有较轻的血小板减少、消耗性凝血障碍和肝损伤并伴有血栓和较低的聚乳酸产生。这些结果表明，C5与凝血功能紊乱、聚乳酸的产生和栓塞性肝损伤有关。总之，C5促进了与组蛋白诱导的致命性血栓形成相关的肝损伤。
Extracellular histones promote platelet aggregation and thrombosis; this is followed by induction of coagulation disorder, which results in exhaustion of coagulation factors. Complement component 5 (C5) is known to be associated with platelet aggregation and coagulation system activation. To date, the pathological mechanism underlying liver injury has remained unclear. Here, we investigated whether C5 promotes liver injury associated with histone-induced lethal thrombosis. C5-sufficient and C5-deficient mice received single tail vein injections of purified, unfractionated histones obtained from calf thymus (45–75 μg/g). Subsequently, the mice were monitored for survival for up to 72 h. Based on the survival data, the 45 μg/g dose was used for analysis of blood cell count, liver function, blood coagulation ability, and promotion of platelet aggregation and platelet/leukocyte aggregate (PLA) production by extracellular histones. C5-deficient mice were protected from lethal thrombosis and had milder thrombocytopenia, consumptive coagulopathy, and liver injury with embolism and lower PLA production than C5-sufficient mice. These results indicate that C5 is associated with coagulation disorders, PLA production, and embolism-induced liver injury. In conclusion, C5 promotes liver injury associated with histone-induced lethal thrombosis.