KFU. Card publication. Neutrophil Extracellular Traps Promote Platelet-Driven Contraction of Inflammatory Blood Clots via Local Generation of Endogenous Thrombin and Softening of the Fibrin Network

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NEUTROPHIL EXTRACELLULAR TRAPS PROMOTE PLATELET-DRIVEN CONTRACTION OF INFLAMMATORY BLOOD CLOTS VIA LOCAL GENERATION OF ENDOGENOUS THROMBIN AND SOFTENING OF THE FIBRIN NETWORK

Form of presentation

Articles in international journals and collections

Year of publication

2025

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Authors, employees of KFU

Salyakhutdinova Shakhnoza Matmuradovna, author

Khabirova Alina Ilshatovna, author

Khismatullin Rafael Rafikovich, author

Other authors

Weisel John W., author

Litvinov Rustem Igorevich, author

Authors, postgraduates KFU

Salyakhutdinova Shakhnoza Matmuradovna, postgraduate kfu

Bibliographic description in the original language

Saliakhutdinova, S.M.; Khismatullin, R.R.; Khabirova, A.I.; Litvinov, R.I.; Weisel, J.W. Neutrophil Extracellular Traps Promote Platelet-Driven Contraction of Inflammatory Blood Clots via Local Generation of Endogenous Thrombin and Softening of the Fibrin Network. Cells 2025, 14, 2018. https://doi.org/10.3390/cells14242018

Annotation

Immunothrombosis can substantially affect the course and outcomes of severe infections and immune-mediated diseases. While inflammatory thrombi are neutrophil-rich, impact of neutrophils on clot contraction, a key modulator of thrombus stability and obstructiveness, was unknown. This study investigated how neutrophils and neutrophil extracellular traps (NETs) affect the rate and extent of platelet-driven clot contraction. Isolated human neutrophils were stimulated with phorbol-12-myristate-13-acetate (PMA) to induce NETosis, confirmed by fluorescence microscopy and scanning electron microscopy. Thrombin-induced clots, formed from whole blood or platelet-rich plasma, were supplemented with non-activated or PMA-activated neutrophils. Clot contraction kinetics and viscoelasticity were analyzed. PMA-activated neutrophils significantly enhanced the rate and final extent of clot contraction compared to controls. This promoting effect was abolished by deoxyribonuclease (DNAse) I, confirming that it was mediated by NETs embedded in the fibrin network. The factor Xa inhibitor rivaroxaban also abrogated this effect, indicating a role for NET-induced endogenous thrombin generation and platelet hyperactivation. Thromboelastography revealed that NETs made clots softer and more deformable. We conclude that activated neutrophils promote clot contraction via NETs embedded in the fibrin network, which enhance platelet contractility via endogenous thrombin production and increase clot deformability, suggesting that inflammatory thrombosis may require treatments addressing this enhanced contractility.

Keywords

neutrophils, neutrophil extracellular traps, clot retraction, immunothrombosis

The name of the journal

CELLS

URL

https://www.mdpi.com/2073-4409/14/24/2018

Please use this ID to quote from or refer to the card

https://repository.kpfu.ru/eng/?p_id=321795&p_lang=2

Resource files

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Full metadata record

Field DC	Value	Language
dc.contributor.author	Salyakhutdinova Shakhnoza Matmuradovna	ru_RU
dc.contributor.author	Khabirova Alina Ilshatovna	ru_RU
dc.contributor.author	Khismatullin Rafael Rafikovich	ru_RU
dc.contributor.author	Weisel John W.	ru_RU
dc.contributor.author	Litvinov Rustem Igorevich	ru_RU
dc.contributor.author	Salyakhutdinova Shakhnoza Matmuradovna	ru_RU
dc.date.accessioned	2025-01-01T00:00:00Z	ru_RU
dc.date.available	2025-01-01T00:00:00Z	ru_RU
dc.date.issued	2025	ru_RU
dc.identifier.citation	Saliakhutdinova, S.M.; Khismatullin, R.R.; Khabirova, A.I.; Litvinov, R.I.; Weisel, J.W. Neutrophil Extracellular Traps Promote Platelet-Driven Contraction of Inflammatory Blood Clots via Local Generation of Endogenous Thrombin and Softening of the Fibrin Network. Cells 2025, 14, 2018. https://doi.org/10.3390/cells14242018	ru_RU
dc.identifier.uri	https://repository.kpfu.ru/eng/?p_id=321795&p_lang=2	ru_RU
dc.description.abstract	CELLS	ru_RU
dc.description.abstract	Immunothrombosis can substantially affect the course and outcomes of severe infections and immune-mediated diseases. While inflammatory thrombi are neutrophil-rich, impact of neutrophils on clot contraction, a key modulator of thrombus stability and obstructiveness, was unknown. This study investigated how neutrophils and neutrophil extracellular traps (NETs) affect the rate and extent of platelet-driven clot contraction. Isolated human neutrophils were stimulated with phorbol-12-myristate-13-acetate (PMA) to induce NETosis, confirmed by fluorescence microscopy and scanning electron microscopy. Thrombin-induced clots, formed from whole blood or platelet-rich plasma, were supplemented with non-activated or PMA-activated neutrophils. Clot contraction kinetics and viscoelasticity were analyzed. PMA-activated neutrophils significantly enhanced the rate and final extent of clot contraction compared to controls. This promoting effect was abolished by deoxyribonuclease (DNAse) I, confirming that it was mediated by NETs embedded in the fibrin network. The factor Xa inhibitor rivaroxaban also abrogated this effect, indicating a role for NET-induced endogenous thrombin generation and platelet hyperactivation. Thromboelastography revealed that NETs made clots softer and more deformable. We conclude that activated neutrophils promote clot contraction via NETs embedded in the fibrin network, which enhance platelet contractility via endogenous thrombin production and increase clot deformability, suggesting that inflammatory thrombosis may require treatments addressing this enhanced contractility.	ru_RU
dc.language.iso	ru	ru_RU
dc.subject	neutrophils	ru_RU
dc.subject	neutrophil extracellular traps	ru_RU
dc.subject	clot retraction	ru_RU
dc.subject	immunothrombosis	ru_RU
dc.title	Neutrophil Extracellular Traps Promote Platelet-Driven Contraction of Inflammatory Blood Clots via Local Generation of Endogenous Thrombin and Softening of the Fibrin Network	ru_RU
dc.type	Articles in international journals and collections	ru_RU