Blood clotting is like a play with many actors. When a blood vessel is damaged, the body needs to seal the injury. Some of the actors play parts in building the clot structure that eventually seals the wound, while others regulate local inflammation.
One actor, a complex molecule called von Willebrand Factor or VWF, plays both types of roles, according to research from RCSI University of Health Sciences. This insight could lead to new ways to help people who have disorders of blood clotting and of the immune system.
For around half a century we have known that VWF, which is the largest protein in the blood, has an important function in helping blood cells called platelets to stick at sites of injury to build up the clot that is needed to stop bleeding. More recently, there had been clues that VWF had other roles too, particularly in controlling how the immune system responds to the injury.
Research led by Professor James O’Donnell, Director of the Irish Centre for Vascular Biology at the RCSI School of Pharmacy and Biomolecular Sciences, shows how VWF interacts with macrophages, a type of immune cell that moves rapidly to regions of injury in the body. In this interaction, VWF encourages the macrophages to sound the alarm more widely about the injury to the blood vessel. So while VWF is acting as a glue to help platelets stick to the newly forming clot, it also marshals more resources to tend to the ailing blood vessel beyond this initial ‘sticking plaster’ structure.
These insights about VWF’s role in influencing macrophages are published in Nature Communications. The study’s findings outline how the blood-clotting factor fires up macrophages and results in chemical signals going out to recruit more immune cells and responses. Understanding more about the biological mechanisms paves the way for exploring ways to focus on VWF for new treatments in clotting and inflammatory disorders.
The research, which was funded by Science Foundation Ireland and the National Institutes of Health (NIH) was carried out by RCSI in collaboration with Trinity College Dublin and the National Coagulation Centre in St James’s Hospital, Dublin.
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