Antithrombin regulates neutrophil activities through the stimulation of C-type lectin family 1A

{"title":"Antithrombin regulates neutrophil activities through the stimulation of C-type lectin family 1A","authors":"Yohei Takahashi ,&nbsp;Soe Soe Htwe ,&nbsp;Dengli Wang ,&nbsp;Hidenori Wake ,&nbsp;Mariko Yata ,&nbsp;Nahoko Tomonobu ,&nbsp;Rie Kinoshita ,&nbsp;Masakiyo Sakaguchi ,&nbsp;Masahiro Nishibori","doi":"10.1016/j.bvth.2024.100032","DOIUrl":null,"url":null,"abstract":"<div><h3>Abstract</h3><div>It has been suggested that a serine proteinase inhibitor, antithrombin (AT), exerts anti-inflammatory effects on different types of cells, independent of thrombin inhibition. In this study, we aimed to identify a specific receptor for AT by a screening method using a transmembrane–tethered AT ligand expressed on HEK293T cells together with the coexpression of candidate receptors, followed by the immunoprecipitation of a complex of AT ligand with a receptor. We identified C-type lectin family 1A (CLEC1A) as a receptor for AT. We confirmed the binding of AT to the extracellular domain of CLEC1A using surface plasmon resonance. Recombinant as well as native AT concentration-dependently induced the rounding of purified human neutrophils in shape, associated with the suppression of spontaneous reactive oxygen species production in vitro, but argatroban did not, indicating the independence of AT effects on thrombin inhibition. Native AT maintained the passage of neutrophils through the artificial microcapillaries. Both AT enhanced the phagocytosis of pHrodo-labeled <em>Escherichia coli</em> and prolonged the viability of the neutrophils. The cellular effects of AT were similar to those of histidine-rich glycoprotein, which has the same CLEC1A as a receptor, and were partially inhibited by the addition of anti-CLEC1A antibody to the incubation media. These results suggested that CLEC1A is a novel receptor for AT, and the stimulation of CLEC1A by AT at least in part mediates the important functional changes of human neutrophils.</div></div>","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"2 1","pages":"Article 100032"},"PeriodicalIF":0.0000,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Blood Vessels, Thrombosis & Hemostasis","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2950327224000329","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}