title: 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.
authors.affiliation: Department of General Internal Medicine and Clinical Laboratory Medicine, Akita University Graduate School of Medicine, Akita, Japan; Divisions of Allergy and Inflammation and Infectious Diseases, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass. Electronic address: ueki-shige@nifty.com.
authors.forename: Shigeharu
authors.initials: S
authors.lastname: Ueki
authors.affiliation: Department of General Internal Medicine and Clinical Laboratory Medicine, Akita University Graduate School of Medicine, Akita, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Konno
authors.affiliation: Department of General Internal Medicine and Clinical Laboratory Medicine, Akita University Graduate School of Medicine, Akita, Japan.
authors.forename: Masahide
authors.initials: M
authors.lastname: Takeda
authors.affiliation: Department of General Internal Medicine and Clinical Laboratory Medicine, Akita University Graduate School of Medicine, Akita, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Moritoki
authors.affiliation: Department of General Internal Medicine and Clinical Laboratory Medicine, Akita University Graduate School of Medicine, Akita, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Hirokawa
authors.affiliation: Department of Otorhinolaryngology, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Matsuwaki
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Akita University Graduate School of Medicine, Akita, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Honda
authors.affiliation: Department of Otorhinolaryngology, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Ohta
authors.affiliation: Cell Analysis Center, Scientific Affairs, Sysmex Corporation, Kobe, Japan.
authors.forename: Shiori
authors.initials: S
authors.lastname: Yamamoto
authors.affiliation: Cell Analysis Center, Scientific Affairs, Sysmex Corporation, Kobe, Japan.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Takagi
authors.affiliation: Cell Analysis Center, Scientific Affairs, Sysmex Corporation, Kobe, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Wada
authors.affiliation: Divisions of Allergy and Inflammation and Infectious Diseases, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass.
authors.forename: Peter F
authors.initials: PF
authors.lastname: Weller
mesh_terms: D002176:Candida albicans; D016923:Cell Death; D004802:Eosinophilia / Q000276:immunology; D004804:Eosinophils / Q000276:immunology; D004926:Escherichia coli; D065206:Extracellular Traps / Q000276:immunology*; D006801:Humans; D009077:Mucins / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D010447:Peptide Hydrolases / Q000276:immunology; D012220:Rhinitis / Q000276:immunology; D012852:Sinusitis / Q000276:immunology; D013211:Staphylococcus aureus
chemical_list: D009077:Mucins; D010447:Peptide Hydrolases
keywords: Eosinophilic chronic rhinosinusitis; eosinophils; extracellular DNA traps; extracellular trap cell death; neutrophils