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

Abhishek Chauhan (), Lozan Sheriff, Mohammed T. Hussain, Gwilym J. Webb, Daniel A. Patten, Emma L. Shepherd, Robert Shaw, Christopher J. Weston, Debashis Haldar, Samuel Bourke, Rajan Bhandari, Stephanie Watson, David H. Adams, Steve P. Watson and Patricia F. Lalor
Additional contact information
Abhishek Chauhan: University of Birmingham
Lozan Sheriff: University of Birmingham
Mohammed T. Hussain: University of Birmingham
Gwilym J. Webb: University of Birmingham
Daniel A. Patten: University of Birmingham
Emma L. Shepherd: University of Birmingham
Robert Shaw: University of Birmingham
Christopher J. Weston: University of Birmingham
Debashis Haldar: University of Birmingham
Samuel Bourke: University of Birmingham
Rajan Bhandari: University of Birmingham
Stephanie Watson: University of Birmingham
David H. Adams: University of Birmingham
Steve P. Watson: University of Birmingham
Patricia F. Lalor: University of Birmingham

Nature Communications, 2020, vol. 11, issue 1, 1-12

Abstract: Abstract 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.

Date: 2020
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-020-15584-3 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15584-3

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-15584-3

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().