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

ABSTRACT: BACKGROUND: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.

SUBMITTER: Ueki S

PROVIDER: S-EPMC4674385 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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

Ueki Shigeharu S Konno Yasunori Y Takeda Masahide M Moritoki Yuki Y Hirokawa Makoto M Matsuwaki Yoshinori Y Honda Kohei K Ohta Nobuo N Yamamoto Shiori S Takagi Yuri Y Wada Atsushi A Weller Peter F PF

The Journal of allergy and clinical immunology 20150609 1

<h4>Background</h4>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.<h4>Objective</h4>We investigated the presence of ETosis-de ...[more]

PMID: 26070883

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Project description:IntroductionNeutrophil extracellular traps (NETs) are structures released by neutrophils in response to various infections. NETs have a biocidal role and have been demonstrated to be effective against bacteria, fungi, viruses, and parasites. Depending on the situation, NETs can protect the host from pathogen invasion or contribute to the development of autoimmune diseases such as cystic fibrosis and rheumatoid arthritis. In this study, we aimed to investigate the occurrence of NET as one of the components in upper respiratory tract secretions in infectious and allergic diseases.MethodsNasal mucus was collected from donors diagnosed with infectious rhinitis or allergic rhinitis. The extracellular DNA content was determined using SytoxGreen staining, and the total protein pool was determined using the microBCA method. Micrococcal nuclease was used to digest the samples and ELISA was employed to identify the NET proteins. The enzymatic activity of elastase was determined.ResultsOur findings showed that nasal mucus collected from patients with infectious rhinosinusitis contained extracellular DNA that could come from a variety of sources, responsible for increasing the density and viscosity of secretions, as well as NETs proteins. The identified enzymatic activity of NET elastase indicates the possible irritation of nasal tissues. However, the DNA content was not identified in the samples from allergic patients. In addition, we have shown in preliminary studies that therapy using N-acetylcysteine can liquefy nasal secretions.DiscussionThe study suggests that the composition of nasal mucus varies according to the cause of mucosal irritation. The presence of DNA and NET proteins can have severe consequences for the therapeutic process prolonging treatment. The low viscosity of nasal mucus in allergic patients facilitates mucosal flushing and the removal of allergens. Understanding the occurrence and role of NETs in various respiratory diseases is critical for developing effective treatment strategies that consider the complex interaction between the immune system and pathogens. The results of this study suggest that NETs may be present in upper respiratory tract secretions with an infectious background, supporting basic defense mechanisms using eosinophils and EETs. Further research is needed to explore the potential of NETs as a therapeutic target in respiratory diseases.

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

Publications

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

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