Neutrophils can promote clotting via FXI and impact clot structure via neutrophil extracellular traps in a distinctive manner in vitro
Abstract Neutrophils and neutrophil extracellular traps (NETs) have been shown to be involved in coagulation. However, the interactions between neutrophils or NETs and fibrin(ogen) in clots, and the mechanisms behind these interactions are not yet fully understood. In this in vitro study, the role o...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-01-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-81268-7 |
| _version_ | 1818996430427127808 |
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| author | Y. Shi J. S. Gauer S. R. Baker H. Philippou S. D. Connell R. A. S. Ariëns |
| author_facet | Y. Shi J. S. Gauer S. R. Baker H. Philippou S. D. Connell R. A. S. Ariëns |
| author_sort | Y. Shi |
| collection | DOAJ |
| description | Abstract Neutrophils and neutrophil extracellular traps (NETs) have been shown to be involved in coagulation. However, the interactions between neutrophils or NETs and fibrin(ogen) in clots, and the mechanisms behind these interactions are not yet fully understood. In this in vitro study, the role of neutrophils or NETs on clot structure, formation and dissolution was studied with a combination of confocal microscopy, turbidity and permeation experiments. Factor (F)XII, FXI and FVII-deficient plasmas were used to investigate which factors may be involved in the procoagulant effects. We found both neutrophils and NETs promote clotting in plasma without the addition of other coagulation triggers, but not in purified fibrinogen, indicating that other factors mediate the interaction. The procoagulant effects of neutrophils and NETs were also observed in FXII- and FVII-deficient plasma. In FXI-deficient plasma, only the procoagulant effects of NETs were observed, but not of neutrophils. NETs increased the density of clots, particularly in the vicinity of the NETs, while neutrophils-induced clots were less stable and more porous. In conclusion, NETs accelerate clotting and contribute to the formation of a denser, more lysis resistant clot architecture. Neutrophils, or their released mediators, may induce clotting in a different manner to NETs, mediated by FXI. |
| first_indexed | 2024-12-20T21:29:37Z |
| format | Article |
| id | doaj.art-6d8af3e1ea2342bb99fc1b951eeda736 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-20T21:29:37Z |
| publishDate | 2021-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-6d8af3e1ea2342bb99fc1b951eeda7362022-12-21T19:26:04ZengNature PortfolioScientific Reports2045-23222021-01-0111111210.1038/s41598-021-81268-7Neutrophils can promote clotting via FXI and impact clot structure via neutrophil extracellular traps in a distinctive manner in vitroY. Shi0J. S. Gauer1S. R. Baker2H. Philippou3S. D. Connell4R. A. S. Ariëns5LIGHT Laboratories, Discovery and Translational Science Department, Institute of Cardiovascular and Metabolic Medicine, University of LeedsLIGHT Laboratories, Discovery and Translational Science Department, Institute of Cardiovascular and Metabolic Medicine, University of LeedsLIGHT Laboratories, Discovery and Translational Science Department, Institute of Cardiovascular and Metabolic Medicine, University of LeedsLIGHT Laboratories, Discovery and Translational Science Department, Institute of Cardiovascular and Metabolic Medicine, University of LeedsThe Astbury Centre for Structural Molecular Biology, Molecular & Nanoscale Physics, University of LeedsLIGHT Laboratories, Discovery and Translational Science Department, Institute of Cardiovascular and Metabolic Medicine, University of LeedsAbstract Neutrophils and neutrophil extracellular traps (NETs) have been shown to be involved in coagulation. However, the interactions between neutrophils or NETs and fibrin(ogen) in clots, and the mechanisms behind these interactions are not yet fully understood. In this in vitro study, the role of neutrophils or NETs on clot structure, formation and dissolution was studied with a combination of confocal microscopy, turbidity and permeation experiments. Factor (F)XII, FXI and FVII-deficient plasmas were used to investigate which factors may be involved in the procoagulant effects. We found both neutrophils and NETs promote clotting in plasma without the addition of other coagulation triggers, but not in purified fibrinogen, indicating that other factors mediate the interaction. The procoagulant effects of neutrophils and NETs were also observed in FXII- and FVII-deficient plasma. In FXI-deficient plasma, only the procoagulant effects of NETs were observed, but not of neutrophils. NETs increased the density of clots, particularly in the vicinity of the NETs, while neutrophils-induced clots were less stable and more porous. In conclusion, NETs accelerate clotting and contribute to the formation of a denser, more lysis resistant clot architecture. Neutrophils, or their released mediators, may induce clotting in a different manner to NETs, mediated by FXI.https://doi.org/10.1038/s41598-021-81268-7 |
| spellingShingle | Y. Shi J. S. Gauer S. R. Baker H. Philippou S. D. Connell R. A. S. Ariëns Neutrophils can promote clotting via FXI and impact clot structure via neutrophil extracellular traps in a distinctive manner in vitro Scientific Reports |
| title | Neutrophils can promote clotting via FXI and impact clot structure via neutrophil extracellular traps in a distinctive manner in vitro |
| title_full | Neutrophils can promote clotting via FXI and impact clot structure via neutrophil extracellular traps in a distinctive manner in vitro |
| title_fullStr | Neutrophils can promote clotting via FXI and impact clot structure via neutrophil extracellular traps in a distinctive manner in vitro |
| title_full_unstemmed | Neutrophils can promote clotting via FXI and impact clot structure via neutrophil extracellular traps in a distinctive manner in vitro |
| title_short | Neutrophils can promote clotting via FXI and impact clot structure via neutrophil extracellular traps in a distinctive manner in vitro |
| title_sort | neutrophils can promote clotting via fxi and impact clot structure via neutrophil extracellular traps in a distinctive manner in vitro |
| url | https://doi.org/10.1038/s41598-021-81268-7 |
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