Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, 46010 Valencia, Spain.
Departamento de Fisiología, Facultad de Medicina y Odontología, Universitat de València, 46010 València, Spain.
Cells. 2022 Dec 15;11(24):4070. doi: 10.3390/cells11244070.
NETosis is a key host immune process against a pathogenic infection during innate immune activation, consisting of a neutrophil "explosion" and, consequently, NET formation, containing mainly DNA, histones, and other nuclear proteins. During sepsis, an exacerbated immune host response to an infection occurs, activating the innate immunity and NETosis events, which requires histone H3 citrullination. Our group compared the circulating histone levels with those citrullinated H3 levels in plasma samples of septic patients. In addition, we demonstrated that citrullinated histones were less cytotoxic for endothelial cells than histones without this post-translational modification. Citrullinated histones did not affect cell viability and did not activate oxidative stress. Nevertheless, citrullinated histones induced an inflammatory response, as well as regulatory endothelial mechanisms. Furthermore, septic patients showed elevated levels of circulating citrullinated histone H3, indicating that the histone citrullination is produced during the first stages of sepsis, probably due to the NETosis process.
NETosis 是固有免疫激活过程中针对病原体感染的关键宿主免疫过程，由中性粒细胞“爆发”和随后的 NET 形成组成，主要包含 DNA、组蛋白和其他核蛋白。在脓毒症中，宿主对感染的过度免疫反应会激活固有免疫和 NETosis 事件，这需要组蛋白 H3 瓜氨酸化。我们的研究小组比较了脓毒症患者血浆样本中循环组蛋白水平与瓜氨酸化 H3 水平。此外，我们还证明了与未经这种翻译后修饰的组蛋白相比，瓜氨酸化组蛋白对内皮细胞的细胞毒性更小。瓜氨酸化组蛋白不会影响细胞活力，也不会激活氧化应激。然而，瓜氨酸化组蛋白诱导了炎症反应以及调节性内皮机制。此外，脓毒症患者表现出循环瓜氨酸化组蛋白 H3 水平升高，表明组蛋白瓜氨酸化是在脓毒症的早期阶段产生的，可能是由于 NETosis 过程。
