Up to 25 million Americans suffer from gallstones. Unwanted stones form in the gallbladder and can grow to the size of a golf ball. They can block the bile ducts and cause severe abdominal pain, infections and even death.
Doctors have known for decades that they appear when excess cholesterol and calcium salts accumulate in the bile – a yellowish-brown liquid that helps the small intestine break down lipids . What kept the particles together to form the stones, however, remained a mystery.
In a study published Wednesday in the journal Immunity, the researchers shed light on the mystery glue. They report that white blood cells called neutrophils are found behind the rock formations. The discovery suggests new potential treatments for the disease.
Solve the mystery
A team of German researchers has tried to find the mystery by examining the composition of the "gallbladder vase", which has a charming name, a type of digestive fluid left too long in the gallbladder and can begin to form gallstones. Like detectives on a crime scene, scientists have discovered traces of DNA and other molecules associated with the most common type of white blood cells, neutrophils.
Neutrophils are the first responders in the body; they protect us against infections. Like spiders catching their prey, neutrophils build web-like structures called extracellular neutrophil traps, better known as NETs, that capture and kill the microorganisms that make us sick. The DNA fragments and molecules discovered by the researchers on the sludge surface belonged to NETs. This suggested that they could play a role in forming painful accretions.
Join the points
To see if NETs were actually involved in gallstones, researchers mixed and shaken human calculations with neutrophils. During the experiment, gallstones rapidly accumulated DNA fragments from neutrophils of the NET building. Preventing neutrophils that mix to make NETs, however, prevented the stones from accumulating more DNA, which implies that they did not get fat.
The team then examined whether NETs were helping gallstones to form as well. To do this, they fed mice with a diet high in cholesterol, induced by the formation of gallstones. Mice with specific genetic defects that prevented the formation of NETs had both fewer and fewer gallstones than healthy mice fed the same diet, they discovered. Similarly, mice with fewer neutrophils in the blood formed smaller gallstones than their normal counterparts.
In another set of experiments, the researchers treated mice in a diet that induced gallstones with drugs to block NET formation or neutrophil migration into the gall bladder. Both treatments resulted in a significant decrease in the size and quantity of stones.
New potential treatment
NETs are a crucial weapon in our defense system against infections. However, previous studies have associated with autoimmune and inflammatory disorders. "We bring here further evidence of the double-edged nature of these nets showing that they play an important role in the assembly and growth of gallstones," said Martin Herrmann, lead author of Immunity study, in a press release.
The discovery opens a new route of treatment for gallstone disease. Although most people do not have symptoms related to their gallstones, those who do usually need surgery to be able to remove them. Drugs that target the formation of NETs, which already exist, could become an effective treatment to avoid surgery.
Establishing new treatments for gallstone disease, however, will require human studies. "Hopefully we can convince drug companies to do a clinical study with [NET inhibitors]"Said Luis Muñoz, one of the main authors of the study, in the press release.