For such a common condition, very little is known about the formation or composition of gallstones. While they’re made up of microscopic crystals of cholesterol and calcium, how they come to be bound together into stones was a mystery, one that researchers at University of Erlangen-Nuremberg have just shed some light on.
The Department of Medicine analysed bile and gallstones from a variety of sources, from operating theatres to abattoirs to a hospital museum. In doing so they discovered that the stones were covered in traces of neutrophil granulocytes, the most common type of white blood cell in the body.
From this the researchers hypothesized that neutrophils attack crystals like they would bacteria or pathogens, in the process covering them in a weblike network of their DNA called a neutrophil extracellular trap (NET). Once covered, the crystals clump together forming stones.
The theory was supported when this process was observed in an experiment that placed netrophils and gallstones into bile. The stones quickly accumulated DNA fragments, until the neutrophils were blocked from making NETs. Strong evidence suggesting that this process also begins the formation of gallstones was provided by a series of experiments on mice. The full results are published in the journal Immunity.
These new insights provide new opportunities for the treatment of gallstone disease. Previously treatment was limited to dietary changes which limit the formation of gallstones, or surgical removal once stones are starting to, or are likely to start causing pain, organ damage or infection. Although they will of course need to be trialed in humans, existing drugs targeting NET formation could provide a pharmacological treatment that avoids the need for surgery, not only for gallstones but kidney and salivary stones as well.
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