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Okayama University identifies specific receptor for the plasma protein antithrombin

2024.11.27

A research group led by Specially-Appointed Professor (Professor Emeritus) Masahiro Nishibori, Professor Masakiyo Sakaguchi, and Visiting Researcher Yohei Takahashi at the Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences has identified C-type lectin family 1A (CLEC1A) as a specific receptor for antithrombin, a plasma protein with anti-inflammatory effects. The results were published in Blood VTH.

Morphological changes in human neutrophils caused by antithrombin (scanning electron micrograph).
Provided by Masahiro Nishibori, Okayama University

Antithrombin has been reported to have anti-inflammatory effects and regulate thrombin activity through direct binding to thrombin. However, the substance involved in its molecular mechanism of action was completely unknown.

In a previous study on the plasma protein HRG, Nishibori's research group has successfully identified a novel HRG-specific receptor. Based on an analogous idea, they hypothesized that there is a plasma membrane receptor associated with anti-inflammatory effects of antithrombin. They used a screening method originally developed by Professor Sakaguchi's research group to search for and identify a novel receptor for antithrombin and analyze its functions. Antithrombin ligand and candidate receptor genes were co-expressed in HEK293T cells, and candidate receptors bound by the ligand were identified through immunoprecipitation. As a result, CLEC1A was identified as a candidate receptor for antithrombin.

Stimulation of CLEC1A on human neutrophil cells by antithrombin induced morphological changes of neutrophils to a spherical shape with a smooth and regular surface and functionally decreased neutrophil death and reactive oxygen species production. They also demonstrated the involvement of the antithrombin−CLEC1A system in the anti-inflammatory effects of antithrombin. These cellular effects of antithrombin are very similar to those of HRG, for which CLEC1A also serves as a receptor, suggesting a completely new functional role and mechanism of action for the plasma proteins.

Journal Information
Publication: Blood Vessels, Thrombosis & Hemostasis
Title: Antithrombin regulates neutrophil activities through the stimulation of C-type lectin family 1A
DOI: 10.1016/j.bvth.2024.100032

This article has been translated by JST with permission from The Science News Ltd. (https://sci-news.co.jp/). Unauthorized reproduction of the article and photographs is prohibited.

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