Organ distribution of histones after intravenous infusion of FITC histones or after sepsis.

Organ distribution of histones after intravenous infusion of FITC histones or after sepsis.
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DOI:
10.1007/s12026-015-8628-2
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发表时间:
2015-03
影响因子:
4.4
通讯作者:
Ward, Peter A.
Ward, Peter A.
中科院分区:
医学4区
文献类型:
--
作者:
Fattahi, Fatemeh;Grailer, Jamison J.;Jajou, Lawrence;Zetoune, Firas S.;Andjelkovic, Anuska V.;Ward, Peter A.

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组蛋白在感染性或非感染性脓毒症期间出现在血浆中,并且与多器官损伤相关。在目前的研究中,组蛋白的静脉输注导致其在主要器官中的定位。在体外小鼠巨噬细胞暴露于组蛋白引起组蛋白的细胞膜上的积累,然后定位到细胞质和细胞核中。多微生物脓毒症(盲肠结扎穿孔,CLP)后,组蛋白出现在血浆中,以及在多器官模式,在8小时达到峰值,然后下降。在肺中,组蛋白和中性粒细胞一起出现,有证据表明形成了中性粒细胞胞外陷阱(NET),这代表了捕获和杀死细菌和其他感染因子的先天免疫反应。在肝脏中,有强烈的NET形成,具有包含组蛋白和DNA链的线性模式。当中性粒细胞在体外用C5 a或佛波醇肉豆蔻酸酯乙酸酯激活时,NET形成随之发生。虽然NET的形成代表感染因子的捕获和杀死,但同时从嗜中性粒细胞释放组蛋白通常导致组织/器官损伤。
Histones appear in plasma during infectious or non-infectious sepsis and are associated with multiorgan injury. In the current studies, intravenous infusion of histones resulted in their localization in major organs. In vitro exposure of mouse macrophages to histones caused a buildup of histones on cell membranes followed by localization into cytosol and into the nucleus. After polymicrobial sepsis (cecal ligation and puncture, CLP), histones appeared in plasma as well as in a multiorgan pattern, peaking at 8 hr followed by decline. In lungs, histones and neutrophils appeared together, with evidence for formation of neutrophil extracellular traps (NETs), which represent an innate immune response to trap and kill bacteria and other infectious agents. In liver, there was intense NET formation, featuring linear patterns containing histones and strands of DNA. When neutrophils were activated in vitro with C5a or phorbol myristate acetate, NET formation ensued. While formation of NETs represents entrapment and killing of infectious agents, the simultaneous release from neutrophils of histones often results in tissue/organ damage.
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