Neutrophils Shown to Play the Key Role in Gallstone Formation

GEN | August 19, 2019

Sticky meshworks of DNA and proteins extruded by neutrophils act as the glue that binds together calcium and cholesterol crystals during gallstone formation, according to scientists in Germany who published a study Neutrophil Extracellular Traps Initiate Gallstone Formation in Immunity. Both genetic and pharmacological approaches that inhibited the formation of these so-called neutrophil extracellular traps NETs reduced the formation and growth of gallstones in mice. 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. 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, the investigators wrote. 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.

Spotlight

A full description of the lifecycle of Karenia brevis could lead to improved monitoring, prediction, and mitigation of the harmful algal blooms it regularly causes.

Spotlight

A full description of the lifecycle of Karenia brevis could lead to improved monitoring, prediction, and mitigation of the harmful algal blooms it regularly causes.

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