Enzymatic lipid oxidation by eosinophils propagates coagulation, hemostasis, and thrombotic disease
| Autor: | Uderhardt, Stefan, Ackermann, Jochen, 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, Diete, 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 |
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| Rok vydání: | 2016 |
| Předmět: |
Adult
Blotting Western Arachidonate 12-Lipoxygenase Risk Factors Hydroxyeicosatetraenoic Acids Animals Arachidonate 15-Lipoxygenase Humans Prospective Studies Blood Coagulation Cells Cultured Aged Mice Knockout Hemostasis Reverse Transcriptase Polymerase Chain Reaction Phosphatidylethanolamines Eosinophil Cationic Protein Thrombin Correction Thrombosis Middle Aged Atherosclerosis R1 Lipids Eosinophils Mice Inbred C57BL Logistic Models Oxidation-Reduction |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| Popis: | 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. Here we demonstrate an unexpected role of eosinophils during plasmatic coagulation, hemostasis and thrombosis. Using a large-scale epidemiological approach, we identified eosinophil cationic protein (ECP) as 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, which relied on the enzymatic generation and active provision of a pro-coagulant phospholipid-surface enriched in 12/15-lipoxygenase (12/15-LO)-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. |
| Databáze: | OpenAIRE |
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