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Enzymatic lipid oxidation by eosinophils propagates coagulation, hemostasis, and thrombotic disease.
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.
Afiliación
  • Uderhardt S; Department of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany.
  • Ackermann JA; Nikolaus Fiebiger Center of Molecular Medicine, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany.
  • Fillep T; Department of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany.
  • Hammond VJ; Nikolaus Fiebiger Center of Molecular Medicine, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany.
  • Willeit J; Department of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany.
  • Santer P; Nikolaus Fiebiger Center of Molecular Medicine, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany.
  • Mayr M; Systems Immunity Research Institute, School of Medicine, Cardiff University, Cardiff, Wales, UK.
  • Biburger M; Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, Wales, UK.
  • Miller M; Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
  • Zellner KR; Bruneck Hospital, Bruneck, Italy.
  • Stark K; King's British Heart Foundation Centre, Kings College, London, England, UK.
  • Zarbock A; Department of Biology, Institute of Genetics, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany.
  • Rossaint J; Medizinische Klinik und Poliklinik I, Klinikum der Universität, Ludwig-Maximilians-Universität, Munich, Germany.
  • Schubert I; Department of Biochemistry and Molecular Biology, Division of Pulmonary Medicine, Mayo Clinic in Arizona, Scottsdale, AZ.
  • Mielenz D; Medizinische Klinik und Poliklinik I, Klinikum der Universität, Ludwig-Maximilians-Universität, Munich, Germany.
  • Dietel B; Department of Anaesthesiology, Intensive Care, and Pain Medicine, University Hospital Münster, Münster, Germany.
  • Raaz-Schrauder D; Department of Anaesthesiology, Intensive Care, and Pain Medicine, University Hospital Münster, Münster, Germany.
  • Ay C; Medizinische Klinik und Poliklinik I, Klinikum der Universität, Ludwig-Maximilians-Universität, Munich, Germany.
  • Gremmel T; Department of Internal Medicine 3, Division of Molecular Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany.
  • Thaler J; Nikolaus Fiebiger Center of Molecular Medicine, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany.
  • Heim C; Department of Cardiology and Angiology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany.
  • Herrmann M; Department of Cardiology and Angiology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany.
  • Collins PW; Department of Medicine I, Clinical Division of Haematology and Haemostaseology, Medical University of Vienna, Vienna, Austria.
  • Schabbauer G; Department of Internal Medicine II, Division of Angiology, Medical University of Vienna, Vienna, Austria.
  • Mackman N; Department of Medicine I, Clinical Division of Haematology and Haemostaseology, Medical University of Vienna, Vienna, Austria.
  • Voehringer D; Department of Cardiac Surgery, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany.
  • Nadler JL; Department of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany.
  • Lee JJ; Systems Immunity Research Institute, School of Medicine, Cardiff University, Cardiff, Wales, UK.
  • Massberg S; Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, Wales, UK.
  • Rauh M; Institute for Physiology, Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.
  • Kiechl S; Department Medicine, University of North Carolina, Chapel Hill, NC.
  • Schett G; Department of Infection Biology, Institute for Clinical Microbiology, Immunology, and Hygiene, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany.
  • O'Donnell VB; Department of Internal Medicine, Eastern Virginia Medical School, Norfolk, VA.
  • Krönke G; Department of Biochemistry and Molecular Biology, Division of Pulmonary Medicine, Mayo Clinic in Arizona, Scottsdale, AZ.
J Exp Med ; 214(7): 2121-2138, 2017 Jul 03.
Article en En | MEDLINE | ID: mdl-28566277
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trombosis / Coagulación Sanguínea / Araquidonato 12-Lipooxigenasa / Araquidonato 15-Lipooxigenasa / Eosinófilos / Hemostasis / Lípidos Tipo de estudio: Diagnostic_studies / Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Animals / Humans / Middle aged Idioma: En Revista: J Exp Med Año: 2017 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trombosis / Coagulación Sanguínea / Araquidonato 12-Lipooxigenasa / Araquidonato 15-Lipooxigenasa / Eosinófilos / Hemostasis / Lípidos Tipo de estudio: Diagnostic_studies / Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Animals / Humans / Middle aged Idioma: En Revista: J Exp Med Año: 2017 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos