Eosinophil extracellular trap cell death-derived DNA traps: Their presence in secretions and functional attributes.
Eosinophil extracellular trap cell death-derived DNA traps: Their presence in secretions and functional attributes.
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DOI：
10.1016/j.jaci.2015.04.041
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发表时间：
2016-01
期刊：
影响因子：
--
通讯作者：
Weller PF
中科院分区：
文献类型：
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作者：
Ueki S;Konno Y;Takeda M;Moritoki Y;Hirokawa M;Matsuwaki Y;Honda K;Ohta N;Yamamoto S;Takagi Y;Wada A;Weller PF
活化的嗜酸性粒细胞和中性粒细胞可以通过细胞溶解性胞外陷阱细胞死亡（ETosis）释放胞外染色质形成DNA陷阱。虽然中性粒细胞DNA陷阱的形成在各种炎症条件下都是公认的，但在人类过敏性疾病中既没有etosis衍生的嗜酸性粒细胞DNA陷阱的存在，也没有研究过这些DNA陷阱的特征。我们研究了嗜酸性粒细胞丰富的鼻窦和耳部分泌物中是否存在ETosis衍生的DNA陷阱，以及ETosis DNA陷阱的功能属性。对嗜酸性慢性鼻窦炎（ECRS）和嗜酸性中耳炎（EOM）患者的富嗜酸性粒细胞分泌物进行了显微镜观察。体外ETosis和DNA陷阱形成的研究使用了血源性嗜酸性粒细胞和中性粒细胞，DNA陷阱的结合能力使用了标记细菌和荧光微珠。荧光显微镜观察了DNA捕集器的稳定性。在体内嗜酸性分泌物中形成了大量携带核组蛋白h1的DNA陷阱，并增加了它们的粘度。在体外，经过短暂的剪切流动，嗜酸性粒细胞etosis诱导的DNA陷阱组装形成稳定的聚集体。嗜酸性细胞DNA通过疏水相互作用捕获细菌和真菌的微珠。与中性粒细胞来源的DNA陷阱相比，嗜酸性粒细胞DNA陷阱在超微结构上表现出更厚的纤维和球状结构，并且不太容易受到白细胞来源的蛋白水解降解，可能是由于嗜酸性粒细胞的蛋白酶活性较低。在人类过敏性疾病中，嗜酸性粒细胞的局部细胞溶解不仅释放游离的嗜酸性粒细胞颗粒，而且还产生核源性DNA陷阱，这是富嗜酸性粒细胞分泌物中的主要细胞外结构成分。
Activated human eosinophils, as well as neutrophils, can release extracellular chromatin to form DNA traps through cytolytic extracellular trap cell death (ETosis). Although formations of neutrophil DNA traps are recognized in various inflammatory conditions, neither the presence of ETosis-derived eosinophil DNA traps in human allergic diseases nor the characteristics of these DNA traps have been studied. We investigated the presence of ETosis-derived DNA traps in eosinophil-rich sinus and ear secretions and the functional attributes of ETosis DNA traps. Eosinophil-rich secretions obtained from patients with eosinophilic chronic rhinosinusitis (ECRS) and eosinophilic otitis media (EOM) were studied microscopically. In vitro studies of ETosis and DNA trap formation used blood-derived eosinophils and neutrophils, and binding capacities of DNA traps used labeled bacteria and fluorescent microbeads. Stabilities of DNA traps were evaluated by fluorescence microscopy. Abundant nuclear histone H1-bearing DNA traps had formed in vivo in the eosinophilic secretions and contributed to their increased viscosity. In vitro, following brief shear flow, eosinophil ETosis-elicited DNA traps assembled to form stable aggregates. Eosinophil DNA traps entrapped bacteria and fungi and by hydrophobic interactions microbeads. In comparison with neutrophil-derived DNA traps, eosinophil DNA traps ultrastructurally exhibited thicker fibers with globular structures and were less susceptible to leukocyte-derived proteolytic degradation, likely due to the lesser protease activities of eosinophils. In human allergic diseases, the local cytolysis of eosinophils not only releases free eosinophil granules but also generates nuclear-derived DNA traps that are major extracellular structural components within eosinophil-rich secretions.