Shigeharu Ueki1, Yasunori Konno2, Masahide Takeda2, Yuki Moritoki2, Makoto Hirokawa2, Yoshinori Matsuwaki3, Kohei Honda4, Nobuo Ohta5, Shiori Yamamoto6, Yuri Takagi6, Atsushi Wada6, Peter F Weller7. 1. 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. 2. Department of General Internal Medicine and Clinical Laboratory Medicine, Akita University Graduate School of Medicine, Akita, Japan. 3. Department of Otorhinolaryngology, Jikei University School of Medicine, Tokyo, Japan. 4. Department of Otorhinolaryngology, Head and Neck Surgery, Akita University Graduate School of Medicine, Akita, Japan. 5. Department of Otorhinolaryngology, Yamagata University School of Medicine, Yamagata, Japan. 6. Cell Analysis Center, Scientific Affairs, Sysmex Corporation, Kobe, Japan. 7. Divisions of Allergy and Inflammation and Infectious Diseases, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass.
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.
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 humanallergic 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 humanallergic 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: Josiane S Neves; Sandra A C Perez; Lisa A Spencer; Rossana C N Melo; Lauren Reynolds; Ionita Ghiran; Salahaddin Mahmudi-Azer; Solomon O Odemuyiwa; Ann M Dvorak; Redwan Moqbel; Peter F Weller Journal: Proc Natl Acad Sci U S A Date: 2008-11-18 Impact factor: 11.205
Authors: D Kang; J Nishida; A Iyama; Y Nakabeppu; M Furuichi; T Fujiwara; M Sekiguchi; K Takeshige Journal: J Biol Chem Date: 1995-06-16 Impact factor: 5.157
Authors: Constantin F Urban; David Ermert; Monika Schmid; Ulrike Abu-Abed; Christian Goosmann; Wolfgang Nacken; Volker Brinkmann; Peter R Jungblut; Arturo Zychlinsky Journal: PLoS Pathog Date: 2009-10-30 Impact factor: 6.823