Journal article

HMGB1 binds to activated platelets via the receptor for advanced glycation end products and is present in platelet rich human coronary artery thrombi

Ingo Ahrens, Yung-Chih Chen, Danijal Topcic, Michael Bode, David Haenel, Christoph E Hagemeyer, Hannah Seeba, Daniel Duerschmied, Nicole Bassler, Karin A Jandeleit-Dahm, Matthew J Sweet, Alex Agrotis, Alex Bobik, Karlheinz Peter

Thrombosis and Haemostasis | SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN | Published : 2015

Abstract

High mobility group box 1 (HMGB1) acts as both a nuclear protein that regulates gene expression, as well as a pro-inflammatory alarmin that is released from necrotic or activated cells. Recently, HMGB1-expression in human atherosclerotic plaques was identified. Therapeutic blockade of HMGB1 reduced the development of diet-induced atherosclerosis in ApoE knockout mice. Thus, we hypothesised an interaction between HMGB1 and activated platelets. Binding of recombinant HMGB1 to platelets was assessed by flow cytometry. HMGB1 bound to thrombin-activated human platelets (MFI 2.49 vs 25.01, p=0.0079). Blood from wild-type, TLR4 and RAGE knockout mice was used to determine potential HMGB1 receptors ..

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Grants

Awarded by NHMRC of Australia


Awarded by German Research Foundation


Funding Acknowledgements

This work has been supported by the NHMRC of Australia (Project Grant 472632, Bobik A, Peter K, Agrotis A), the Australian Research Council and the German Research Foundation (AH 185/1-1, Ahrens I). We thank Dr Keyue Liu and Dr Masahiro Nishbori for providing the monoclonal anti-KLH antibody for the immunohistochemistry.