The platelet receptor CLEC-2 blocks neutrophil mediated hepatic recovery in acetaminophen induced acute liver failure


Acetaminophen (APAP) is the main cause of acute liver failure in the West. Specific efficacious therapies for acute liver failure (ALF) are limited and time-dependent. The mechanisms that drive irreversible acute liver failure remain poorly characterized. Here we report that the recently discovered platelet receptor CLEC-2 (C-type lectin-like receptor) perpetuates and worsens liver damage after toxic liver injury. Our data demonstrate that blocking platelet CLEC-2 signalling enhances liver recovery from acute toxic liver injuries (APAP and carbon tetrachloride) by increasing tumour necrosis factor-α (TNF-α) production which then enhances reparative hepatic neutrophil recruitment. We provide data from humans and mice demonstrating that platelet CLEC-2 influences the hepatic sterile inflammatory response and that this can be manipulated for therapeutic benefit in acute liver injury. Since CLEC-2 mediated platelet activation is independent of major haemostatic pathways, blocking this pathway represents a coagulopathy-sparing, specific and novel therapy in acute liver failure.

Publication DOI:
Divisions: College of Health & Life Sciences > School of Biosciences
College of Health & Life Sciences
Additional Information: © The Author(s) 2020 This article is licensed under a Creative Commons Attribution 4.0 International License, to view a copy of this license, visit
Uncontrolled Keywords: Acetaminophen/adverse effects,Animals,Blood Platelets/immunology,Carbon Tetrachloride/adverse effects,Chemical and Drug Induced Liver Injury/etiology,Humans,Lectins, C-Type/genetics,Liver/drug effects,Mice,Mice, Inbred C57BL,Neutrophils/immunology,Tumor Necrosis Factor-alpha/genetics
Publication ISSN: 2041-1723
Full Text Link:
Related URLs: https://www.nat ... nal-information (Publisher URL)
PURE Output Type: Article
Published Date: 2020-04-22
Accepted Date: 2020-03-17
Authors: Chauhan, Abhishek
Sheriff, Lozan
Hussain, Mohammed T
Webb, Gwilym J
Patten, Daniel A
Shepherd, Emma Louise (ORCID Profile 0000-0002-1345-1746)
Shaw, Robert K
Weston, Christopher J
Haldar, Debashis
Bourke, Samuel
Bhandari, Rajan
Watson, Stephanie
Adams, David H.
Watson, Steve P.
Lalor, Patricia F.



Version: Published Version

License: Creative Commons Attribution

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