Neutrophil Extracellular Traps Initiate Gallstone Formation

Munoz LE, Boeltz S, Bilyy R, Schauer C, Mahajan A, Widulin N, Grüneboom A, Herrmann I, Boada E, Rauh M, Krenn V, Biermann MH, Podolska M, Hahn J, Knopf J, Maueröder C, Paryzhak S, Dumych T, Zhao Y, Neurath M, Hoffmann M, Fuchs TA, Leppkes M, Schett G, Herrmann M (2019)

Publication Type: Journal article

Publication year: 2019

Journal

Immunity Elsevier

Book Volume: 51

Pages Range: 443-450.e4

Journal Issue: 3

DOI: 10.1016/j.immuni.2019.07.002

Abstract

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.

Authors with CRIS profile

Luis Munoz Becerra Department of Medicine 3 – Rheumatology and Immunology Aparna Mahajan Department of Medicine 3 – Rheumatology and Immunology Manfred Rauh Department of Paediatrics and Adolescent Medicine Malgorzata Podolska Department of Medicine 3 – Rheumatology and Immunology Jonas Hahn Department of Medicine 3 – Rheumatology and Immunology Jasmin Knopf Department of Medicine 3 – Rheumatology and Immunology Christian Maueröder Department of Medicine 3 – Rheumatology and Immunology Markus Neurath Lehrstuhl für Innere Medizin I Markus Hoffmann Department of Medicine 3 – Rheumatology and Immunology Georg Schett Lehrstuhl für Innere Medizin III Martin Herrmann Department of Medicine 3 – Rheumatology and Immunology

Involved external institutions

Danylo Halytsky Lviv National Medical University / Львiвський Національний Медичний Унiверситет iм. Данила Галицького UA Ukraine (UA) Universitätsklinikum Hamburg-Eppendorf (UKE) DE Germany (DE) West China Medical Center of Sichuan University / 四川大学华西医学中心 CN China (CN) Universität Trier DE Germany (DE) Charité - Universitätsmedizin Berlin DE Germany (DE)

How to cite

APA:

Munoz, L.E., Boeltz, S., Bilyy, R., Schauer, C., Mahajan, A., Widulin, N.,... Herrmann, M. (2019). Neutrophil Extracellular Traps Initiate Gallstone Formation. Immunity, 51(3), 443-450.e4. https://doi.org/10.1016/j.immuni.2019.07.002

MLA:

Munoz, Luis Enrique, et al. "Neutrophil Extracellular Traps Initiate Gallstone Formation." Immunity 51.3 (2019): 443-450.e4.

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