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Impaired DNase1-mediated degradation of neutrophil extracellular traps is associated with acute thrombotic microangiopathies

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Impaired DNase1-mediated degradation of neutrophil extracellular traps is associated with acute thrombotic microangiopathies. / Jiménez-Alcázar, M; Napirei, M; Panda, R; Köhler, E C; Kremer Hovinga, J A; Mannherz, H G; Peine, S; Renné, T; Lämmle, B; Fuchs, T A.

in: J THROMB HAEMOST, Jahrgang 13, Nr. 5, 05.2015, S. 732-42.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Jiménez-Alcázar, M, Napirei, M, Panda, R, Köhler, EC, Kremer Hovinga, JA, Mannherz, HG, Peine, S, Renné, T, Lämmle, B & Fuchs, TA 2015, 'Impaired DNase1-mediated degradation of neutrophil extracellular traps is associated with acute thrombotic microangiopathies', J THROMB HAEMOST, Jg. 13, Nr. 5, S. 732-42. https://doi.org/10.1111/jth.12796

APA

Jiménez-Alcázar, M., Napirei, M., Panda, R., Köhler, E. C., Kremer Hovinga, J. A., Mannherz, H. G., Peine, S., Renné, T., Lämmle, B., & Fuchs, T. A. (2015). Impaired DNase1-mediated degradation of neutrophil extracellular traps is associated with acute thrombotic microangiopathies. J THROMB HAEMOST, 13(5), 732-42. https://doi.org/10.1111/jth.12796

Vancouver

Jiménez-Alcázar M, Napirei M, Panda R, Köhler EC, Kremer Hovinga JA, Mannherz HG et al. Impaired DNase1-mediated degradation of neutrophil extracellular traps is associated with acute thrombotic microangiopathies. J THROMB HAEMOST. 2015 Mai;13(5):732-42. https://doi.org/10.1111/jth.12796

Bibtex

@article{1f72ab9a3d0f4c50926828c51402a70d,
title = "Impaired DNase1-mediated degradation of neutrophil extracellular traps is associated with acute thrombotic microangiopathies",
abstract = "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.METHODS 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 indicate 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.",
keywords = "Deoxyribonuclease I, Extracellular Traps, Humans, Hydrolysis, Neutrophils, Thrombotic Microangiopathies",
author = "M Jim{\'e}nez-Alc{\'a}zar and M Napirei and R Panda and K{\"o}hler, {E C} and {Kremer Hovinga}, {J A} and Mannherz, {H G} and S Peine and T Renn{\'e} and B L{\"a}mmle and Fuchs, {T A}",
note = "{\textcopyright} 2014 International Society on Thrombosis and Haemostasis.",
year = "2015",
month = may,
doi = "10.1111/jth.12796",
language = "English",
volume = "13",
pages = "732--42",
journal = "J THROMB HAEMOST",
issn = "1538-7933",
publisher = "Wiley-Blackwell",
number = "5",

}

RIS

TY - JOUR

T1 - Impaired DNase1-mediated degradation of neutrophil extracellular traps is associated with acute thrombotic microangiopathies

AU - Jiménez-Alcázar, M

AU - Napirei, M

AU - Panda, R

AU - Köhler, E C

AU - Kremer Hovinga, J A

AU - Mannherz, H G

AU - Peine, S

AU - Renné, T

AU - Lämmle, B

AU - Fuchs, T A

N1 - © 2014 International Society on Thrombosis and Haemostasis.

PY - 2015/5

Y1 - 2015/5

N2 - 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.METHODS 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 indicate 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.

AB - 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.METHODS 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 indicate 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.

KW - Deoxyribonuclease I

KW - Extracellular Traps

KW - Humans

KW - Hydrolysis

KW - Neutrophils

KW - Thrombotic Microangiopathies

U2 - 10.1111/jth.12796

DO - 10.1111/jth.12796

M3 - SCORING: Journal article

C2 - 25418346

VL - 13

SP - 732

EP - 742

JO - J THROMB HAEMOST

JF - J THROMB HAEMOST

SN - 1538-7933

IS - 5

ER -