High content of dietary fructose stimulates the formation of neutrophil extracellular traps in the biliary system

Abstract

Neutrophils safeguard our bloodstreams as well as the surface of ducts, mucosa linings and wounds, intending to protect us from pathogens. Bile ducts connect the bacteria-filled intestine with the liver, the metabolic factory of the body, full of sinusoidal capillaries. Thus, bile ducts become a hot place in the body, requiring constant protection from pathogens. Neutrophils can us three ways: they can phagocytize pathogens, produce chemicals mediate pathogens` to form neutrophil extracellular traps (NETs). The latter decondensed DNA fibers, decorated components of neutrophilic granules abundant ROS production. NETs the but, and examined for the presence of NETs by visualizing DNA content with PI by means of the fluorescence microscopy. Under both HFD and HLHCD conditions we observed the formation of NETs in the gallbladder. Serum, obtained from blood samples, was analyzed for the activity of neutrophil elastase (an enzyme released from neutrophilic granules upon NETs formation) by using specific fluorogenic substrate. Neutrophil elastase activity was significantly increased after 6 weeks of feeding on the HFD (p=0.0219) and HLHCD (p=0.0148, ANOVA). Thus, we can conclude that high dietary fructose content stimulates the formation of neutrophil extracellular traps in bile ducts of experimental animals. These findings are extremely important in understanding the reasons for low-grade inflammation observed under non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH).