Eosinophil extracellular trap cell death-derived DNA traps: Their presence in secretions and functional attributes

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• 作者：Shigeharu Ueki ; MD ; PhD^a ; ^b ; ^{ueki-shige@nifty.com" class="auth_mail" title="E-mail the corresponding author} ; Yasunori Konno ; DDS^a ; Masahide Takeda ; MD ; PhD^a ; Yuki Moritoki ; MD ; PhD^a ; Makoto Hirokawa ; MD ; PhD^a ; Yoshinori Matsuwaki ; MD ; PhD^c ; Kohei Honda ; MD ; PhD^d ; Nobuo Ohta ; MD ; PhD^e ; Shiori Yamamoto ; BSA^f ; Yuri Takagi^f ; Atsushi Wada ; PhD^f ; Peter F. Weller ; MD^b
• 关键词：Eosinophilic chronic rhinosinusitis ; eosinophils ; extracellular trap cell death ; extracellular DNA traps ; neutrophils
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：137
• 期：1
• 页码：258-267
• 全文大小：3657 K

文摘

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 patients with 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.

Objective

We investigated the presence of ETosis-derived DNA traps in eosinophil-rich sinus and ear secretions and the functional attributes of ETosis DNA traps.

Methods

Eosinophil-rich secretions obtained from patients with eosinophilic chronic rhinosinusitis and eosinophilic otitis media were studied microscopically. In vitro studies of ETosis and DNA trap formation used blood-derived eosinophils and neutrophils, and studies of the binding capacities of DNA traps used labeled bacteria and fluorescent microbeads. Stabilities of DNA traps were evaluated by using fluorescence microscopy.

Results

Abundant nuclear histone H1–bearing DNA traps formed in vivo in the eosinophilic secretions and contributed to their increased viscosity. In vitro, after brief shear flow, eosinophil ETosis-elicited DNA traps assembled to form stable aggregates. Eosinophil DNA traps entrapped bacteria and fungi and, through 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 because of the lesser protease activities of eosinophils.

Conclusions

In human allergic diseases 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.