Details

Autor(en) / Beteiligte

• 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

Titel

Neutrophil Extracellular Traps Initiate Gallstone Formation

Ist Teil von

• Immunity (Cambridge, Mass.), 2019-09, Vol.51 (3), p.443-450.e4

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2019

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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. •Gallstones contain extracellular DNA and neutrophil-derived granular enzymes•Neutrophils form extended aggregates of gallstone building blocks in vitro•Uptake of crystals by neutrophils causes lysosomal leakage and NET formation•NOX2 and PADI4 activities are required for the generation and growth of gallstones Cholelithiasis, the presence of gallstones in the gallbladder or ducts, is a prevalent human disease with a high socioeconomic burden. Muñoz and colleagues demonstrate that the formation of neutrophil extracellular traps fosters the generation and growth of gallstones.