Iba Toshiaki, Murai Miwa, Nagaoka Isao, Tabe Yoko
Department of Emergency and Disaster Medine Graduate School of Medicine, Juntendo University Tokyo Japan.
Department of Host Defense and Biochemical Research Graduate School of Medicine, Juntendo University Tokyo Japan.
Acute Med Surg. 2013 Nov 15;1(1):2-9. doi: 10.1002/ams2.10. eCollection 2014 Jan.
In addition to pathogen-associated molecular patterns from invasive microorganisms, alarmins, which are major components of host defense mechanisms, are involved in the pathophysiology of sepsis. In fact, the magnitude of the insult is defined according to the damage-associated molecular pattern (DAMP), which is composed of alarmins as well as pathogen-associated molecular patterns, such as those involving nucleosomes, histones, and DNA. Regarding the antimicrobial mechanism of neutrophils, an alternative non-phagocytic mechanism was first recognized as "NETosis" in 2004. In this mechanism, microorganisms are trapped and eliminated by neutrophil extracellular traps (NETs). These NETs are composed of histones and DNA that have been expelled from the nucleus as well as antimicrobial proteases, including elastase and myeloperoxidase. NETosis, a cell death pathway reported to be distinct from apoptosis, is an active area of research. As NETs are composed of deleterious substances, they are extremely harmful to the host cells once they are released into the circulating blood. Therefore, the meanings and putative roles of these components in sepsis have attracted much attention.
除了来自侵袭性微生物的病原体相关分子模式外,警报素作为宿主防御机制的主要组成部分,也参与了脓毒症的病理生理学过程。事实上,损伤的严重程度是根据损伤相关分子模式(DAMP)来定义的,DAMP由警报素以及病原体相关分子模式组成,比如涉及核小体、组蛋白和DNA的模式。关于中性粒细胞的抗菌机制,一种替代性的非吞噬机制于2004年首次被确认为“NETosis”。在这种机制中,微生物被中性粒细胞胞外诱捕网(NETs)捕获并清除。这些NETs由从细胞核排出的组蛋白和DNA以及包括弹性蛋白酶和髓过氧化物酶在内的抗菌蛋白酶组成。NETosis是一种据报道与凋亡不同的细胞死亡途径,是一个活跃的研究领域。由于NETs由有害物质组成,一旦释放到循环血液中,它们对宿主细胞极具危害性。因此,这些成分在脓毒症中的意义和假定作用备受关注。