We’re all familiar with acute inflammation – the redness, pain and bruising around injuries that alerts the immune system to the damage it needs to heal. However, if this response becomes prolonged, chronic inflammation can then see healthy tissue attacked and the risk of serious illness becomes increasingly greater.
More than 50% of all deaths across the globe are linked to chronic inflammation-related diseases such as ischemic heart disease, cancer, stroke, diabetes mellitus, kidney disease, non-alcoholic fatty liver disease and autoimmune and neurodegenerative conditions. And there are very few interventions for chronic inflammation beyond diet and lifestyle changes.
Now, researchers have made a breakthrough discovery, unlocking how white blood cells move from blood vessels to injury sites. This opens the door to the development of treatments that could stop them in their tracks, in turn providing better outcomes for diseases caused by chronic inflammation.
The study out of the Centenary Institute has uncovered the mechanism by which neutrophils "unstick" from blood vessels, which enables them to move around the body. A type of white blood cell, neutrophils are essential components of the immune system and the body’s "first responders" for injury or infection, but too much of a good thing over time can lead to dangerous chronic inflammation conditions.
“Molecules known as integrins help neutrophils stick to the walls of blood vessels, to prevent the cells from being carried away by blood flow,” said Dr. Joyce Chiu, lead author of the study, from the ACRF Centenary Cancer Research Centre at the University of Sydney. “To move to the site of injury, neutrophils must stick and unstick from blood vessel walls. While we knew how integrins helped neutrophils stick, we did not know how they unstick.”
The scientists identified a protein secreted by neutrophils, protein disulfide isomerase (PDI), that plays a pivotal role in enabling the cells to unstick from blood vessels. Dr. Chiu believes that by targeting PDI, the release of neutrophils could be limited.
“New drugs can be designed to inhibit PDI, to keep neutrophils from ‘unsticking’ and migrating from blood vessel walls,” she added. “Preventing neutrophils from moving around can help prevent chronic inflammation by reducing their ability to accumulate at sites of injury or infection."
While neutrophils are, of course, needed in response to injury, limiting their ability to gather and damage healthy tissue could have a big impact on chronic inflammation-related diseases such as heart attack and stroke.
“Our research could pave the way for new treatments and management strategies that are able to limit the extent of inflammation, and potentially improve outcomes for individuals with chronic inflammatory and cardiovascular conditions,” Dr. Chiu said.
The study was published in the journal Circulation Research.
Source: Centenary Institute
