A new-found link between coagulation and inflammation?

Eike Struck
PhD student at TREC

Humans have two very important defense systems. The coagulation system, that forms a clot of blood after wounding to stop bleeding, and the immune system, that defends us against invaders such as viruses and bacteria. In mammals those systems are separated while they are combined in ancient animals, such as the star fish.

Although these two defense systems are separated in humans, they still have some links, as our PhD candidate Ina Isabella Høiland showed in her PhD defense this spring. In a recently published study, Laura Burzynski and her colleagues investigated a previously unknown link between coagulation and inflammation.

This link has been highly conserved throughout evolution and traces back to the defense system of ancient animals. In those animals, coagulation and immune response are activated at the same time.

Interleukin 1α is an important molecule in immune responses. It helps to protect the body against diseases and infections when it is activated during inflammation. Then it helps to recruit white blood cells (immune cells). In their study, Bruzynski and colleagues show that thrombin, an important molecule in the blood clotting mechanism, can activate Interleukin 1α.

But why is this important? The first function of the body during wounding is to stop bleeding. The second function is to stop infections. When we have a wound, bacteria can penetrate into the blood stream. Thrombin is produced when a damaged surface such as a wound needs clotting to prevent blood loss. It helps to form the clot at the site of the wound. Under normal conditions it takes a few minutes to activate the immune response.

If thrombin can activate Interleukin 1α, then a quick response against infection at the site of the wound could be possible. So it makes sense that this process is highly conserved in evolution because having the ability to activate Interleukin 1α at the site of the wound may improve the chance of survival.

Burzynski and colleagues’ data illustrates the importance of this protective mechanism. They inactivated the ability of mice to activate Interleukin 1α through thrombin. The mice that lost this ability had impaired wound healing. Additionally, they had fewer immune cells at the site of the wound. This means interleukin 1α helps to defend the body against invaders and aids in wound healing.

Furthermore, they showed that after acute loss of platelets, blood cells that are responsible for stopping bleeding, Interleukin 1α helps to restore them. This knowledge could be helpful in diseases such as thrombocytopenia, a bleeding disorder characterized by acute loss of thrombocytes.

To fully understand the impact and clinical possibilities of this interesting “crosstalk” between the immune system and coagulation, further research is necessary.

Reference: Burzynski, Laura C., et al. The Coagulation and Immune Systems Are Directly Linked through the Activation of Interleukin-1α by Thrombin. Immunity (2019).

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