B8 The contact system in liver: an interface of inflammation, innate immunity and coagulation

B8_April 2014

Principal Investigator:
Prof. Dr. med. Dr. rer. nat. Thomas Renné
Institut für Klinische Chemie und Laboratoriumsmedizin
Universitätsklinikum Hamburg-Eppendorf
Martinistr. 52
20246 Hamburg
Tel.: +49-40-7410-52981
E-Mail: t.renne@uke.de

Participating Staff:
Dr. rer. nat. Reiner Mailer– Group leader
Prof. Dr. rer. nat. Hartmut Schlüter– Group leader
Dr. med. Verena Kiencke – Resident physician
Maike Voss- BTA
Dr. med. vet. Lorena Hänel- PostDoc
Bastian Plochg – cand. med.

Project description

Combinations of inflammatory and coagulation reactions are the unifying principle underlying a variety of infectious, immune, thrombotic and malignant hepatic disorders. The factor XII-driven contact system and its activator the inorganic polymer polyphosphate are a paradigm to elucidate the nexus of coagulation and inflammation in the liver, in order to improve patient care.

B08 in 60 SecondsVideoarchiv

B08 in 60 Seconds online seit 16.12.2018
Ein Thrombus an den Oxygenatormembranen einer speziellen Herz-Lungenmaschine
Figure 1: A thrombus at the oxygenating membranes of a special heart-lung machine (Kjell Hultenby, Karolinska Stockholm)

In the first funding period we have developed technology to measure polyphosphate in human samples and produced recombinant polyphosphate inhibitors. Infusion of these inhibitors interfered with inflammatory and prothrombotic reactions in murine models.

In our translational project we now aim to analyze roles of polyphosphate for inflammatory, infectious, and malignant liver disease and test interference with polyphosphate activities for healing and therapy. We will analyze mouse models with deficiency and excess polyphosphate activity. Transgenic mice will be challenged in models of liver infection/inflammation, regeneration and cancer. Findings arising from experimental animal models will be compared to patient data using systems biology. The project will provide a comprehensive insight of the polyphosphate/contact system pathway in liver disease states and may offer novel therapies for liver disorders.

Related news:

Nickel KF, Long AT, Fuchs TA, Butler LM, Renné T

Factor XII as a Therapeutic Target in Thromboembolic and Inflammatory Diseases
Arterioscler Thromb Vasc Biol. 2017 Jan;37(1):13-20. doi: 10.1161/ATVBAHA.116.308595.

Labberton L, Kenne E, Long AT, Nickel KF, Di Gennaro A, Rigg RA, Hernandez JS,Butler L, Maas C, Stavrou EX, Renné T

Neutralizing blood-borne polyphosphate in vivo provides safe thromboprotection
Nat Commun. 2016 Sep 6;7:12616. doi:10.1038/ncomms12616

Long AT, Kenne E, Jung R, Fuchs TA, Renné T

Contact system revisited: an interface between inflammation, coagulation, and innate immunity
J Thromb Haemost. 2016 Mar;14(3):427-37. doi: 10.1111/jth.13235. Epub 2016 Feb 9. Review.

Worm M, Köhler EC, Panda R, Long A, Butler LM, Stavrou EX, Nickel KF, Fuchs TA, Renné T

The factor XIIa blocking antibody 3F7: a safe anticoagulant with anti-inflammatory activities
Ann Transl Med. 2015 Oct;3(17):247. doi:10.3978/j.issn.2305-5839.2015.09.07. Review.