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Enzymatic lipid oxidation by eosinophils propagates coagulation, hemostasis, and thrombotic disease.
- Source :
-
The Journal of experimental medicine [J Exp Med] 2017 Jul 03; Vol. 214 (7), pp. 2121-2138. Date of Electronic Publication: 2017 May 31. - Publication Year :
- 2017
-
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.<br /> (© 2017 Uderhardt et al.)
- Subjects :
- Adult
Aged
Animals
Arachidonate 12-Lipoxygenase genetics
Arachidonate 15-Lipoxygenase genetics
Atherosclerosis diagnosis
Atherosclerosis metabolism
Blotting, Western
Cells, Cultured
Eosinophil Cationic Protein metabolism
Humans
Hydroxyeicosatetraenoic Acids metabolism
Logistic Models
Mice, Inbred C57BL
Mice, Knockout
Middle Aged
Oxidation-Reduction
Phosphatidylethanolamines metabolism
Prospective Studies
Reverse Transcriptase Polymerase Chain Reaction
Risk Factors
Thrombin metabolism
Arachidonate 12-Lipoxygenase metabolism
Arachidonate 15-Lipoxygenase metabolism
Blood Coagulation
Eosinophils metabolism
Hemostasis
Lipids analysis
Thrombosis metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1540-9538
- Volume :
- 214
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- The Journal of experimental medicine
- Publication Type :
- Academic Journal
- Accession number :
- 28566277
- Full Text :
- https://doi.org/10.1084/jem.20161070