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Eosinophil ETosis and DNA Traps: a New Look at Eosinophilic Inflammation

  • Shigeharu UekiEmail author
  • Takahiro Tokunaga
  • Shigeharu Fujieda
  • Kohei Honda
  • Makoto Hirokawa
  • Lisa A. Spencer
  • Peter F. Weller
Otitis (D Skoner, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Otitis

Abstract

The traditional paradigm of eosinophils as end-stage damaging cells has mainly relied on their release of cytotoxic proteins. Cytokine-induced cell survival and secretion of granular contents from tissue-dwelling eosinophil are thought to be important mechanisms for eosinophilic inflammatory disorders, although the occurrence of cytolysis and its products (i.e., free extracellular granules) has been observed in affected lesions. Recent evidence indicates that activated eosinophils can exhibit a non-apoptotic cell death pathway, namely extracellular trap cell death (ETosis) that mediates the eosinophil cytolytic degranulation. Here, we discuss the current concept of eosinophil ETosis which provides a new look at eosinophilic inflammation. Lessons from eosinophilic chronic rhinosinusitis revealed that ETosis-derived DNA traps, composed of stable web-like chromatin, contribute to the properties of highly viscous eosinophilic mucin and impairments in its clearance. Intact granules entrapped in DNA traps are causing long-lasting inflammation but also might have immunoregulatory roles. Eosinophils possess a way to have post-postmortem impacts on innate immunity, local immune response, sterile inflammation, and tissue damage.

Keywords

Cytolysis Eosinophilic chronic rhinosinusitis Eosinophils ETosis DNA traps Neutrophils 

Abbreviations

CRS

Chronic rhinosinusitis

CRSwNP

CRS with nasal polyps

CRSsNP

CRS without nasal polyps

DAMP

Damage-associated molecular pattern

ECP

Eosinophil cationic protein

ECRS

Eosinophilic chronic rhinosinusitis

EETs

Eosinophil extracellular traps

EPO

Eosinophil peroxidase

ETosis

Extracellular trap cell death

EETosis

Eosinophil extracellular trap cell death

FEG

Free eosinophil granule

GM-CSF

Granulocyte-macrophage colony-stimulating factor

MBP

Major basic protein

NETosis

Neutrophil extracellular trap cell death

PMA

Phorbol myristate acetate

TSLP

Thymic stromal lymphopoietin

Notes

Acknowledgments

This study was funded in part by Research Grant on Allergic Disease and Immunology from Japan Agency for Medical Research and Development, Charitable Trust Laboratory Medicine Research Foundation of Japan, and JSPS KAKENHI 16 K08926 (SU), Grants-in-Aid for Scientific Research from the Japanese Ministry of Health, Labor and Welfare H27, H28-Research on measures for intractable disease-general-004 (SF), NIH R37-AI020241 (PFW), R01-AI051645 (PFW), and R01-HL095699 (LAS).

Compliance with Ethics Guidelines

Conflict of Interest

Drs. Ueki, Tokunaga, Fujieda, Honda, Hirokawa, Spencer, and Weller declare no conflicts of interest relevant to this manuscript.

Human and Animal Rights and Informed Consent

With regard to the authors’ research cited in this paper, all procedures were followed in accordance with the ethical standards of the responsible committee on human experimentation and with the Helsinki Declaration.

Supplementary material

Supplementary material 1: Video 1

3D image of DNA traps in eosinophilic mucin. Using confocal Z-stacks and 3D reconstruction (Carl Zeiss LSM510 confocal microscope and LSM software, ×63 objective), eosinophil DNA traps were evaluated throughout the depths of eosinophilic mucin. Fixed eosinophilic mucin from surgically obtained ECRS patient was stained with DNA dye SYTOX green (produced from Ref. 37) (MPG 1892 kb)

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Shigeharu Ueki
    • 1
    Email author
  • Takahiro Tokunaga
    • 2
  • Shigeharu Fujieda
    • 2
  • Kohei Honda
    • 3
  • Makoto Hirokawa
    • 1
  • Lisa A. Spencer
    • 4
  • Peter F. Weller
    • 4
  1. 1.Department of General Internal Medicine and Clinical Laboratory MedicineAkita University Graduate School of MedicineAkitaJapan
  2. 2.Department of Otorhinolaryngology, Head and Neck SurgeryUniversity of FukuiFukuiJapan
  3. 3.Department of Otorhinolaryngology, Head and Neck SurgeryAkita Graduate School of MedicineAkitaJapan
  4. 4.Divisions of Allergy and Inflammation and Infectious Diseases, Department of MedicineBeth Israel Deaconess Medical Center, Harvard Medical SchoolBostonUSA

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