The platelet receptor CLEC-2 blocks neutrophil mediated hepatic recovery in acetaminophen induced acute liver failure.
MouseChemical/toxinC57BL/6J; Vav1-iCre and Pf4Cre conditional lines on a C57BL/6J backgroundIntravenous5 micrograms/kg functional grade purified anti-podoplanin24 hours before acetaminophen or carbon tetrachloride administration, pre-treat…
Model: Acetaminophen-induced acute liver injury by single intraperitoneal injection of 350 mg/kg acetaminophen in PBS; a second model used intraperitoneal carbon tetrachloride 1 ml/kg diluted 1:4 in mineral oil
Blocking platelet CLEC-2 signalling reduced hepatocellular damage and transaminase release by increasing hepatic neutrophil recruitment. Protection appeared only at later time points, 24 to 48 hours for acetaminophen, and was abolished by neutrophil depletion or TNF-alpha blockade with etanercept.
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