Ward Peter A, Fattahi Fatemeh, Bosmann Markus
Department of Pathology, University of Michigan Medical School , Ann Arbor, MI , USA.
Center for Thrombosis and Hemostasis, University Medical Center , Mainz , Germany.
Front Immunol. 2016 Mar 9;7:86. doi: 10.3389/fimmu.2016.00086. eCollection 2016.
While the phlogistic activities of IgM or IgG immune complexes (ICs) have been well established as complement-activating agents and seem likely to play important roles in humans with vasculitis, certain types of glomerulonephritis as well as in a variety of autoimmune diseases, the predominant clinical strategies have involved the use of immunosuppressive or anti-inflammatory drugs. Over the past decade, new insights into molecular events developing during IC models in rodents have identified new phlogistic products that may be candidates for therapeutic blockade. Extracellular histones, located in the web-like structures of neutrophil extracellular traps, are released from complement-activated polymorphonuclear neutrophils (PMNs) downstream of IC deposition. Extracellular histones appear to be a new class of highly tissue-damaging products derived from complement-activated PMNs. Histones have also been discovered in cell-free broncho-alveolar lavage fluids from humans with acute respiratory distress syndrome (ARDS). Recent studies emphasize that in the setting of ARDS-like reactions in rodents, extracellular histones are released and are exceedingly proinflammatory, tissue damaging, and prothrombotic. Such studies suggest that in humans with ARDS, extracellular histones may represent therapeutic targets for blockade.
虽然IgM或IgG免疫复合物（ICs）的促炎活性已被充分确认为补体激活剂，并且似乎可能在患有血管炎的人类、某些类型的肾小球肾炎以及各种自身免疫性疾病中发挥重要作用，但主要的临床策略一直是使用免疫抑制或抗炎药物。在过去十年中，对啮齿动物IC模型中发生的分子事件的新见解确定了可能成为治疗性阻断候选物的新促炎产物。位于中性粒细胞胞外陷阱的网状结构中的细胞外组蛋白，是从IC沉积下游补体激活的多形核中性粒细胞（PMN）中释放出来的。细胞外组蛋白似乎是一类新的源自补体激活的PMN的高度组织损伤性产物。在患有急性呼吸窘迫综合征（ARDS）的人类的无细胞支气管肺泡灌洗液中也发现了组蛋白。最近的研究强调，在啮齿动物中类似ARDS反应的情况下，细胞外组蛋白会被释放出来，并且具有极强的促炎、组织损伤和促血栓形成作用。此类研究表明，在患有ARDS的人类中，细胞外组蛋白可能是阻断治疗的靶点。
