Details

Autor(en) / Beteiligte

• Uderhardt, Stefan
• Ackermann, Jochen A
• Fillep, Tobias
• Hammond, Victoria J
• Willeit, Johann
• Santer, Peter
• Mayr, Manuel
• Biburger, Markus
• Miller, Meike
• Zellner, Katie R
• Stark, Konstantin
• Zarbock, Alexander
• Rossaint, Jan
• Schubert, Irene
• Mielenz, Dirk
• Dietel, Barbara
• Raaz-Schrauder, Dorette
• Ay, Cihan
• Gremmel, Thomas
• Thaler, Johannes
• Heim, Christian
• Herrmann, Martin
• Collins, Peter W
• Schabbauer, Gernot
• Mackman, Nigel
• Voehringer, David
• Nadler, Jerry L
• Lee, James J
• Massberg, Steffen
• Rauh, Manfred
• Kiechl, Stefan
• Schett, Georg
• O'Donnell, Valerie B
• Krönke, Gerhard

Titel

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

Ist Teil von

• The Journal of experimental medicine, 2017-07, Vol.214 (7), p.2121-2138

Ort / Verlag

United States: The Rockefeller University Press

Erscheinungsjahr

2017

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.