Jiménez-Alcázar, M; Napirei, M; Panda, R; Köhler, E C; Kremer Hovinga, Johanna Anna; Mannherz, H G; Peine, S; Renné, T; Lämmle, Bernhard; Fuchs, T A (2015). Impaired DNase1-mediated degradation of neutrophil extracellular traps is associated with acute thrombotic microangiopathies. Journal of thrombosis and haemostasis, 13(5), pp. 732-742. Wiley-Blackwell 10.1111/jth.12796
|
Text
2014_J Thr Haem_Impaired jDNase1_Kremer.pdf - Accepted Version Available under License Publisher holds Copyright. Download (509kB) | Preview |
BACKGROUND
Acute thrombotic microangiopathies (TMAs) are characterized by excessive microvascular thrombosis and are associated with markers of neutrophil extracellular traps (NETs) in plasma. NETs are composed of DNA fibers and promote thrombus formation through the activation of platelets and clotting factors.
OBJECTIVE
The efficient removal of NETs may be required to prevent excessive thrombosis such as in TMAs. To test this hypothesis, we investigated whether TMAs are associated with a defect in the degradation of NETs.
APPROACH AND RESULTS
We show that NETs generated in vitro were efficiently degraded by plasma from healthy donors. However, NETs remained stable after exposure to plasma from TMA patients. The inability to degrade NETs was linked to a reduced DNase activity in TMA plasma. Plasma DNase1 was required for efficient NET-degradation and TMA plasma showed decreased levels of this enzyme. Supplementation of TMA plasma with recombinant human DNase1 restored NET-degradation activity.
CONCLUSIONS
Our data indicates that DNase1-mediated degradation of NETs is impaired in patients with TMAs. The role of plasma DNases in thrombosis is, as of yet, poorly understood. Reduced plasma DNase1 activity may cause the persistence of pro-thrombotic NETs and thus promote microvascular thrombosis in TMA patients. This article is protected by copyright. All rights reserved.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Haematology and Central Haematological Laboratory 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Hämatologie (Erwachsene) |
UniBE Contributor: |
Kremer Hovinga Strebel, Johanna Anna, Lämmle, Bernhard |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
1538-7836 |
Publisher: |
Wiley-Blackwell |
Language: |
English |
Submitter: |
Verena Zwahlen |
Date Deposited: |
17 Mar 2015 17:33 |
Last Modified: |
02 Mar 2023 23:26 |
Publisher DOI: |
10.1111/jth.12796 |
PubMed ID: |
25418346 |
Uncontrolled Keywords: |
Deoxyribonuclease I, Neutrophil Extracellular Traps, Neutrophils, Thrombosis, Thrombotic Microangiopathies |
BORIS DOI: |
10.7892/boris.64645 |
URI: |
https://boris.unibe.ch/id/eprint/64645 |
Actions (login required)
 |
Edit item |