Sticky nets of DNA from immune cells may be to blame for gallstones

The team found DNA (red) and an enzyme (green) on the surface of human gallstones (yellow)

Munoz et al./Immunity

It has long been known that gallstones grow from crystals in the gallbladder, but it has been unclear how these stick together. Now it seems immune cells are to blame – a finding that could lead to new treatments.

Martin Herrmann at the Friedrich–Alexander University Erlangen–Nürnberg in Germany and his colleagues made this discovery while studying small stones in the bile of people undergoing operations to treat their gallstones.

On the surface of the small stones were telltale signs of neutrophil extracellular traps – sticky webs of DNA released by immune cells to catch invading microbes. The presence of large clumps of DNA and an enzyme used by neutrophil immune cells suggested that these cells had been targeting bile crystals for attack.

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To test this, the team mixed cholesterol crystals with human neutrophils in the lab. The neutrophils responded by shooting their DNA out at the crystals.

Suspicious matter

When they shook and spun gallstones around in the presence of neutrophils, the gallstone surfaces quickly collected neutrophil DNA. These sticky webs pulled cholesterol and calcium crystals together to form even larger stones.

“When they find suspicious matter, for example the crystals that form gallstones, they tend to eject their DNA and hog-tie the material,” says Herrmann.

The stones formed in this way may go unnoticed until one passes from the gallbladder into the small intestine or lodges in a bile duct, causing sudden and severe pain.

The findings may lead to preventative treatments for gallstones. Herrmann and his colleagues found that altering genes or using drugs to impair the formation of these traps led to fewer and smaller gallstones in mice.

One of the drugs the team tested, called metoprolol, is currently used to treat some heart conditions. Trials in people are needed to see if the drug also helps to prevent gallstones, says Hermann.

Journal reference: Immunity, DOI: 10.1016/j.immuni.2019.07.002

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