Antithrombin study suggests new mechanism of action for functional role of plasma protein

It has been reported that antithrombin, a plasma protein, controls thrombin activity by binding directly to thrombin and also has an anti-inflammatory effect. However, the actual molecular mechanism of antithrombin’s anti-inflammatory effect was completely unknown.

One previous work Professor Nishibori’s research group succeeded in identifying a new HRG-specific receptor on HRG, and based on a similar idea, they hypothesized that antithrombin has a plasma membrane receptor associated with its anti-inflammatory effect.

using a scanning method Developed independently by Professor Sakaguchi’s research group, this team searched for and identified a new receptor for antithrombin and analyzed its function.

Antithrombin ligands and candidate receptor genes were coexpressed in HEK293T cellsand candidate receptors that bind to the ligand were identified by immunoprecipitation.

Research It was published in the magazine Blood Vessels, Thrombosis and Hemostasis.

As a result, CLEC1A was identified as a candidate receptor for antithrombin. Antithrombin stimulates CLEC1A on human neutrophil cells to change the morphology of neutrophils to a spherical shape with a smooth surface and functionally suppresses neutrophil cell death and ROS production.

They also show that the antithrombin-CLEC1A system plays a role. anti-inflammatory effect of antithrombin. This cellular effect of antithrombin is very similar to that of HRG, which has the same receptor as CLEC1A, suggesting a completely new functional role and mechanism of action for it. plasma protein group.

This research suggests cell plasma membrane receptor stimulation, a completely new mechanism of action for the functional role of plasma protein antithrombin. The innovative receptor identification method is not only academically unique, but is also expected to bring about revolutionary changes in plasma protein science through its future application to other plasma protein factors.