Fattahi Fatemeh, Grailer Jamison J, Jajou Lawrence, Zetoune Firas S, Andjelkovic Anuska V, Ward Peter A
Department of Pathology, University of Michigan Medical School, 7520 MSRB I, 1301 Catherine Rd, Ann Arbor, MI, 48109-5602, USA.
Immunol Res. 2015 Mar;61(3):177-86. doi: 10.1007/s12026-015-8628-2.
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), histones appeared in plasma as well as in a multiorgan pattern, peaking at 8 h 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.
在感染性或非感染性脓毒症期间，组蛋白会出现在血浆中，并与多器官损伤相关。在当前的研究中，静脉输注组蛋白会导致它们在主要器官中定位。将小鼠巨噬细胞在体外暴露于组蛋白会导致组蛋白在细胞膜上积聚，随后定位到细胞质和细胞核中。在多微生物脓毒症（盲肠结扎和穿刺）后，组蛋白出现在血浆以及多器官中，在8小时达到峰值，随后下降。在肺部，组蛋白和中性粒细胞同时出现，有证据表明形成了中性粒细胞胞外陷阱（NETs），这代表了一种捕获和杀死细菌及其他感染因子的固有免疫反应。在肝脏中，有强烈的NET形成，其特征是包含组蛋白和DNA链的线性模式。当用C5a或佛波酯肉豆蔻酸酯在体外激活中性粒细胞时，会形成NET。虽然NET的形成代表了对感染因子的捕获和杀伤，但中性粒细胞同时释放组蛋白往往会导致组织/器官损伤。
