A study by Laura Burzynski, a former BHF PhD student and now postdoc in Murray Clarke’s lab (Medicine), reveals a fundamental and unappreciated direct link between the coagulation and immune systems. Although links between inflammation and haemostasis exist in mammals, they are indirect and relatively slow to act. Laura and colleagues discovered that the coagulation protease thrombin directly cleaves interleukin-1α, rapidly activating the downstream inflammatory cascade. This cleavage site in IL-1α is highly conserved throughout mammals, suggesting it confers an important function.
Bleeding is the primary challenge to survival after wounding, followed by the risk of infection. Thus, activation of inflammation during haemostasis would help prevent wound infection. These findings suggest an elegant way for this to occur, with the primary effector of coagulation directly cleaving and activating an apical effector of immunity, leading to the rapid recruitment of immune cells to the wound site.
The work, published in Immunity, also identified thrombin-cleaved IL-1α in patients with sepsis, further suggesting that this new link may be relevant in multiple inflammatory and thrombotic diseases, and normal physiology.