TY - JOUR
T1 - Enzymatic lipid oxidation by eosinophils propagates coagulation, hemostasis, and thrombotic disease
AU - Uderhardt, Stefan
AU - Ackermann, Jochen A.
AU - Fillep, Tobias
AU - Hammond, Victoria J.
AU - Willeit, Johann
AU - Santer, Peter
AU - Mayr, Manuel
AU - Biburger, Markus
AU - Miller, Meike
AU - Zellner, Katie R.
AU - Stark, Konstantin
AU - Zarbock, Alexander
AU - Rossaint, Jan
AU - Schubert, Irene
AU - Mielenz, Dirk
AU - Dietel, Barbara
AU - Raaz-Schrauder, Dorette
AU - Ay, Cihan
AU - Gremmel, Thomas
AU - Thaler, Johannes
AU - Heim, Christian
AU - Herrmann, Martin
AU - Collins, Peter W.
AU - Schabbauer, Gernot
AU - Mackman, Nigel
AU - Voehringer, David
AU - Nadler, Jerry L.
AU - Lee, James J.
AU - Massberg, Steffen
AU - Rauh, Manfred
AU - Kiechl, Stefan
AU - Schett, Georg
AU - O'Donnell, Valerie B.
AU - Krönke, Gerhard
N1 - Publisher Copyright:
© 2017 Uderhardt et al.
PY - 2017/7/1
Y1 - 2017/7/1
N2 - 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.
AB - 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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U2 - 10.1084/jem.20161070
DO - 10.1084/jem.20161070
M3 - Article
C2 - 28566277
AN - SCOPUS:85022006602
SN - 0022-1007
VL - 214
SP - 2121
EP - 2138
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 7
ER -