Platform 3

Platelet Function

Beside their central role in haemostasis and thrombosis platelets are crucially involved in inflammation, arteriosclerosis, angiogenesis, anti-microbial host defense and hematogenous tumour growth/metastasis. The integrity of platelet function is a prerequisite for intact haemostasis but it enables also efficient interaction with other blood and vascular cells leading to functional crosstalk of the interacting partners. Platelets bind to leukocytes und form together heterocellular conjugates in the blood circulation which present a cellular and functional link between the haemostasis and inflammation system.

Ex vivo detection of human platelet-monocyte conjugates in the peripheral blood by flow cytometry (dot plot presentation of single cells and cell-conjugates) and fluorescence microscopy.

Specific platelet function tests provide useful tools for the research of platelet biology and defects, for the clinical diagnosis of platelet-related disorders, for monitoring of haemostatic therapy and individualizing treatment. In addition to the traditional test of platelet aggregometry this platform laboratory provides modern methods to study in detail the

• Activation and functional capacity of single platelets (flow cytometry)
• Platelet-dependent thrombin generation/ coagulation (calibrated automated thrombography)
• Interaction of platelets with other blood / vascular cells, migration and dynamics of thrombus formation in real time under flow (integrated BioFlux-flow chamber system)
• Platelet protein composition and posttranslational modifications (LC-MS-based quantitative platelet proteomics and phospho-proteomics in collaboration with the Insitute of Immunology, Core Facility for Mass Spectrometry, Prof. Dr. Stefan Tenzer

This platform laboratory provides the feasibility for CTH-associated and external collaboration partners to apply modern ex vivo/in vitro methods for research and clinical studies in the field of human/murine platelet phenotyping and function analysis.

In addition, the platform offers methods and expertise for specialized diagnostics of platelet function disorders in collaboration with the Thrombosis Clinic of the CTH and and the MVZ Laboratory Medicine of the University Clinic Mainz.

The diagnostic platform methods are also used to establish ring tests within the framework of THROMKIDplus AG of the GTH Standing Commission on Pediatrics.

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Partners using this method

Partners at the CTH

• Univ.-Prof. Dr. Christoph Reinhardt (Experimental Hemostasis and Gnotobiotics)
• Prof. Dr. Philip Wenzel (Vascular Inflammation)
• Jun. Prof. Dr. Carsten Deppermann (Systems Interactions of Hemostasis)
• PD Dr. Susanne Karbach (Systemic inflammation and vascular disease)
• Guest Scientist of the CTH Prof. Dr. Stepan Gambaryan (Russian Academy of Science, St. Petersburg, Russland)

Partners at the University Medical Center Mainz

• Univ.-Prof. Dr. Katrin Schäfer, Dr. Magdalena Bochenek/CTH Virchow Fellow (Center for Cardiology – Cardiology I)
• Univ.-Prof. Dr. Christine Espinola Klein (Center for Cardiology – Cardiology III/Angiology)
• Univ.-Prof. Dr. Julia Weinmann-Menke (III. Department of Medicine – Nephrology)
• Univ.-Prof. Dr. Volker Mailänder (Department of Dermatology and Polyclinic)
• Prof. Dr. Andrea Tüttenberg (Department of Dermatology and Polyclinic)
• Prof. Dr. Markus Radsak, Dr. Astrid Alflen (III. Department of Medicine)

Further partners and projects

• Univ.-Prof. Dr. Margitta Elvers (Univeristy Medical Center Düsseldorf)
• European joint doctoral degree program TICARDIO (Marie Skłodowska-Curie Innovative Training Networks within Horizon 2020)
• Promicol BV, Geleen, Netherlands

Platform

• This platform is part of the 'Shared Expertise' of the DZHK ('Plattformlobor CTH' - shared expertise SE076)

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Scientific Platform Coordinator

Platform-Supervisor

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References (selection)

• Schonichen C, Montague SJ, Brouns SLN, Burston JJ, Cosemans J, Jurk K, Kehrel BE, Koenen RR, Ni Ainle F, O'Donnell VB, Soehnlein O, Watson SP, Kuijpers MJE, Heemskerk JWM and Nagy M. Antagonistic Roles of Human Platelet Integrin alphaIIbbeta3 and Chemokines in Regulating Neutrophil Activation and Fate on Arterial Thrombi Under Flow. Arterioscler Thromb Vasc Biol. 2023;43:1700-1712.
• Leberzammer J, Agten SM, Blanchet X, Duan R, Ippel H, Megens RTA, Schulz C, Aslani M, Duchene J, Doring Y, Jooss NJ, Zhang P, Brandl R, Stark K, Siess W, Jurk K, Heemskerk JWM, Hackeng TM, Mayo KH, Weber C and von Hundelshausen P. Targeting platelet-derived CXCL12 impedes arterial thrombosis. Blood. 2022;139:2691-2705.
• Jurk K, Rothenaicher KF, Gross K, Rossmann H, Weisser G, Schmidtmann I, Munzel T and Espinola-Klein C. Differential Inhibition of Platelet Reactivity by Dual Therapy With Aspirin and Low-Dose Rivaroxaban in Peripheral Arterial Disease: A Pilot Study. Front Cardiovasc Med. 2022;9:865166.
• Jurk K, Adenaeuer A, Sollfrank S, Gross K, Hauser F, Czwalinna A, Erkel J, Fritsch N, Marandiuc D, Schaller M, Lackner KJ, Rossmann H and Bergmann F. Novel GATA1 Variant Causing a Bleeding Phenotype Associated with Combined Platelet alpha-/delta-Storage Pool Deficiency and Mild Dyserythropoiesis Modified by a SLC4A1 Variant. Cells. 2022;11.
• da Costa Marques R, Simon J, d'Arros C, Landfester K, Jurk K and Mailander V. Proteomics reveals differential adsorption of angiogenic platelet lysate proteins on calcium phosphate bone substitute materials. Regen Biomater. 2022;9:rbac044.
• Rukoyatkina N, Shpakova V, Sudnitsyna J, Panteleev M, Makhoul S, Gambaryan S and Jurk K. Curcumin at Low Doses Potentiates and at High Doses Inhibits ABT-737-Induced Platelet Apoptosis. Int J Mol Sci. 2021;22.
• Zimmer N, Krebs FK, Zimmer S, Mitzel-Rink H, Kumm EJ, Jurk K, Grabbe S, Loquai C and Tuettenberg A. Platelet-Derived GARP Induces Peripheral Regulatory T Cells-Potential Impact on T Cell Suppression in Patients with Melanoma-Associated Thrombocytosis. Cancers (Basel). 2020;12.
• Krueger I, Gremer L, Mangels L, Klier M, Jurk K, Willbold D, Bock HH and Elvers M. Reelin Amplifies Glycoprotein VI Activation and AlphaIIb Beta3 Integrin Outside-In Signaling via PLC Gamma 2 and Rho GTPases. Arterioscler Thromb Vasc Biol. 2020;40:2391-2403.
• Ascher S, Wilms E, Pontarollo G, Formes H, Bayer F, Muller M, Malinarich F, Grill A, Bosmann M, Saffarzadeh M, Brandao I, Gross K, Kiouptsi K, Kittner JM, Lackner KJ, Jurk K and Reinhardt C. Gut Microbiota Restricts NETosis in Acute Mesenteric Ischemia-Reperfusion Injury. Arterioscler Thromb Vasc Biol. 2020;40:2279-2292.
• Kiouptsi K, Jackel S, Pontarollo G, Grill A, Kuijpers MJE, Wilms E, Weber C, Sommer F, Nagy M, Neideck C, Jansen Y, Ascher S, Formes H, Karwot C, Bayer F, Kollar B, Subramaniam S, Molitor M, Wenzel P, Rosenstiel P, Todorov H, Gerber S, Walter U, Jurk K, Heemskerk JWM, van der Vorst EPC, Doring Y and Reinhardt C. The Microbiota Promotes Arterial Thrombosis in Low-Density Lipoprotein Receptor-Deficient Mice. mBio. 2019;10.
• Althaus K, Zieger B, Bakchoul T, Jurk K; THROMKID-Plus Studiengruppe der Gesellschaft für Thrombose- und Hämostaseforschung (GTH) und der Gesellschaft für Pädiatrische Onkologie und Hämatologie (GPOH). Standardization of Light Transmission Aggregometry for Diagnosis of Platelet Disorders: An Inter-Laboratory External Quality Assessment. Thromb Haemost. 2019;119:1154-1161.