Neutrophil Extracellular Traps Initiate Gallstone Formation
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Neutrophil Extracellular Traps Initiate Gallstone Formation. / Muñoz, Luis E; Boeltz, Sebastian; Bilyy, Rostyslav; Schauer, Christine; Mahajan, Aparna; Widulin, Navena; Grüneboom, Anika; Herrmann, Irmgard; Boada, Edgyda; Rauh, Manfred; Krenn, Veit; Biermann, Mona H C; Podolska, Malgorzata J; Hahn, Jonas; Knopf, Jasmin; Maueröder, Christian; Paryzhak, Solomiya; Dumych, Tetiana; Zhao, Yi; Neurath, Markus F; Hoffmann, Markus H; Fuchs, Tobias A; Leppkes, Moritz; Schett, Georg; Herrmann, Martin.
in: IMMUNITY, Jahrgang 51, Nr. 3, 17.09.2019, S. 443-450.e4.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Neutrophil Extracellular Traps Initiate Gallstone Formation
AU - Muñoz, Luis E
AU - Boeltz, Sebastian
AU - Bilyy, Rostyslav
AU - Schauer, Christine
AU - Mahajan, Aparna
AU - Widulin, Navena
AU - Grüneboom, Anika
AU - Herrmann, Irmgard
AU - Boada, Edgyda
AU - Rauh, Manfred
AU - Krenn, Veit
AU - Biermann, Mona H C
AU - Podolska, Malgorzata J
AU - Hahn, Jonas
AU - Knopf, Jasmin
AU - Maueröder, Christian
AU - Paryzhak, Solomiya
AU - Dumych, Tetiana
AU - Zhao, Yi
AU - Neurath, Markus F
AU - Hoffmann, Markus H
AU - Fuchs, Tobias A
AU - Leppkes, Moritz
AU - Schett, Georg
AU - Herrmann, Martin
N1 - Copyright © 2019 Elsevier Inc. All rights reserved.
PY - 2019/9/17
Y1 - 2019/9/17
N2 - The presence of gallstones (cholelithiasis) is a highly prevalent and severe disease and one of the leading causes of hospital admissions worldwide. Due to its substantial health impact, we investigated the biological mechanisms that lead to the formation and growth of gallstones. We show that gallstone assembly essentially requires neutrophil extracellular traps (NETs). We found consistent evidence for the presence of NETs in human and murine gallstones and describe an immune-mediated process requiring activation of the innate immune system for the formation and growth of gallstones. Targeting NET formation via inhibition of peptidyl arginine deiminase type 4 or abrogation of reactive oxygen species (ROS) production, as well as damping of neutrophils by metoprolol, effectively inhibit gallstone formation in vivo. Our results show that after the physicochemical process of crystal formation, NETs foster their assembly into larger aggregates and finally gallstones. These insights provide a feasible therapeutic concept to prevent cholelithiasis in patients at risk.
AB - The presence of gallstones (cholelithiasis) is a highly prevalent and severe disease and one of the leading causes of hospital admissions worldwide. Due to its substantial health impact, we investigated the biological mechanisms that lead to the formation and growth of gallstones. We show that gallstone assembly essentially requires neutrophil extracellular traps (NETs). We found consistent evidence for the presence of NETs in human and murine gallstones and describe an immune-mediated process requiring activation of the innate immune system for the formation and growth of gallstones. Targeting NET formation via inhibition of peptidyl arginine deiminase type 4 or abrogation of reactive oxygen species (ROS) production, as well as damping of neutrophils by metoprolol, effectively inhibit gallstone formation in vivo. Our results show that after the physicochemical process of crystal formation, NETs foster their assembly into larger aggregates and finally gallstones. These insights provide a feasible therapeutic concept to prevent cholelithiasis in patients at risk.
U2 - 10.1016/j.immuni.2019.07.002
DO - 10.1016/j.immuni.2019.07.002
M3 - SCORING: Journal article
C2 - 31422870
VL - 51
SP - 443-450.e4
JO - IMMUNITY
JF - IMMUNITY
SN - 1074-7613
IS - 3
ER -