title: Eosinophil ETosis and DNA Traps: a New Look at Eosinophilic Inflammation.
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.
authors.affiliation: Department of General Internal Medicine and Clinical Laboratory Medicine, Akita University Graduate School of Medicine, 1-1-1, Hondo, Akita, 010-8543, Japan. ueki-shige@nifty.com.
authors.forename: Shigeharu
authors.initials: S
authors.lastname: Ueki
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, University of Fukui, Fukui, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Tokunaga
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, University of Fukui, Fukui, Japan.
authors.forename: Shigeharu
authors.initials: S
authors.lastname: Fujieda
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Akita Graduate School of Medicine, Akita, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Honda
authors.affiliation: Department of General Internal Medicine and Clinical Laboratory Medicine, Akita University Graduate School of Medicine, 1-1-1, Hondo, Akita, 010-8543, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Hirokawa
authors.affiliation: Divisions of Allergy and Inflammation and Infectious Diseases, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Spencer
authors.affiliation: Divisions of Allergy and Inflammation and Infectious Diseases, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Peter F
authors.initials: PF
authors.lastname: Weller
mesh_terms: D004804:Eosinophils / Q000276:immunology* / Q000473:pathology*; D065206:Extracellular Traps / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000276:immunology* / Q000473:pathology
keywords: Cytolysis; DNA traps; ETosis; Eosinophilic chronic rhinosinusitis; Eosinophils; Neutrophils