Enzymatic lipid oxidation by eosinophils propagates coagulation, hemostasis, and thrombotic disease.

Beitrag in einer Fachzeitschrift


Details zur Publikation

Autor(en): Uderhardt S, Ackermann JA, Fillep T, Hammond VJ, Willeit J, Santer P, Mayr M, Biburger M, Miller M, Zellner KR, Stark K, Zarbock A, Rossaint J, Schubert I, Mielenz D, Dietel B, Raaz-Schrauder D, Ay C, Gremmel T, Thaler J, Heim C, Herrmann M, Collins PW, Schabbauer G, Mackman N, Vöhringer D, Nadler JL, Lee JJ, Massberg S, Rauh M, Kiechl S, Schett G, O'Donnell VB, Krönke G
Zeitschrift: Journal of Experimental Medicine
Jahr der Veröffentlichung: 2017
ISSN: 1540-9538


Abstract


Blood coagulation is essential for physiological hemostasis but simultaneously contributes to thrombotic disease. However, molecular and cellular events controlling initiation and propagation of coagulation are still incompletely understood. In this study, we demonstrate an unexpected role of eosinophils during plasmatic coagulation, hemostasis, and thrombosis. Using a large-scale epidemiological approach, we identified eosinophil cationic protein as an independent and predictive risk factor for thrombotic events in humans. Concurrent experiments showed that eosinophils contributed to intravascular thrombosis by exhibiting a strong endogenous thrombin-generation capacity that relied on the enzymatic generation and active provision of a procoagulant phospholipid surface enriched in 12/15-lipoxygenase-derived hydroxyeicosatetraenoic acid-phosphatidylethanolamines. Our findings reveal a previously unrecognized role of eosinophils and enzymatic lipid oxidation as regulatory elements that facilitate both hemostasis and thrombosis in response to vascular injury, thus identifying promising new targets for the treatment of thrombotic disease.



FAU-Autoren / FAU-Herausgeber

Biburger, Markus PD Dr.
Lehrstuhl für Genetik
Dietel, Barbara
Graduiertenzentrum der FAU
Heim, Christian
Herzchirurgische Klinik
Herrmann, Martin Prof. Dr.
Medizinische Klinik 3 - Rheumatologie und Immunologie
Krönke, Gerhard Prof. Dr. med.
Medizinische Klinik 3 - Rheumatologie und Immunologie
Mielenz, Dirk PD Dr.
Medizinische Fakultät
Rauh, Manfred Prof. Dr.
Kinder- und Jugendklinik
Schett, Georg Prof. Dr. med.
Lehrstuhl für Innere Medizin III
Vöhringer, David Prof. Dr.
Infektionsbiologische Abteilung am Mikrobiologischen Institut


Autor(en) der externen Einrichtung(en)
British Heart Foundation (BHF)
Cardiff University
Eastern Virginia Medical School
Klinikum der Universität München (Großhadern und Innenstadt)
Krankenhaus Bruneck / Ospedale di Brunico
Mayo Clinic Phoenix
Medizinische Universität Innsbruck
Medizinische Universität Wien
Universitätsklinikum Münster
University of North Carolina at Chapel Hill


Zitierweisen

APA:
Uderhardt, S., Ackermann, J.A., Fillep, T., Hammond, V.J., Willeit, J., Santer, P.,... Krönke, G. (2017). Enzymatic lipid oxidation by eosinophils propagates coagulation, hemostasis, and thrombotic disease. Journal of Experimental Medicine. https://dx.doi.org/10.1084/jem.20161070

MLA:
Uderhardt, Stefan, et al. "Enzymatic lipid oxidation by eosinophils propagates coagulation, hemostasis, and thrombotic disease." Journal of Experimental Medicine (2017).

BibTeX: 

Zuletzt aktualisiert 2018-06-08 um 23:38