Ticagrelor Exerts Immune-Modulatory Effect by Attenuating Neutrophil Extracellular Traps
Neutrophils through the release of neutrophil extracellular traps (NETs) containing active tissue factor (TF) are key components of thrombo-inflammation. Platelets-neutrophils interplay in ST elevation myocardial infarction (STEMI) promotes NET formation via inorganic polyphosphates (polyP) released...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/10/3625 |
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| author | Alexandros Mitsios Akrivi Chrysanthopoulou Athanasios Arampatzioglou Iliana Angelidou Veroniki Vidali Konstantinos Ritis Panagiotis Skendros Dimitrios Stakos |
| author_facet | Alexandros Mitsios Akrivi Chrysanthopoulou Athanasios Arampatzioglou Iliana Angelidou Veroniki Vidali Konstantinos Ritis Panagiotis Skendros Dimitrios Stakos |
| author_sort | Alexandros Mitsios |
| collection | DOAJ |
| description | Neutrophils through the release of neutrophil extracellular traps (NETs) containing active tissue factor (TF) are key components of thrombo-inflammation. Platelets-neutrophils interplay in ST elevation myocardial infarction (STEMI) promotes NET formation via inorganic polyphosphates (polyP) released by thrombin-activated platelets. NETs, however, are also induced by biomaterials in a platelet-independent manner. Considering the possible pleiotropic effects of Ticagrelor beyond platelet inhibition and the clinical need for novel antithrombotic strategies targeting inflammation, we investigated the effects of Ticagrelor on polyP and stent-induced NETs in STEMI. Neutrophils from healthy individuals and patients receiving Ticagrelor were stimulated with polyP or drug-eluting stents (DES) to produce NETs. To induce TF expression, neutrophils were further incubated with plasma obtained from the infarct-related artery (IRA) of STEMI patients. The effects of Ticagrelor on NETs and TF loading were assessed using fluorescence microscopy, flow cytometry, myeloperoxidase(MPO)/DNA complex ELISA, and a Western blot. Ticagrelor interrupts platelet–neutrophil interaction by attenuating NETs induced by polyP. However, Ticagrelor does not affect polyP secretion from thrombin-activated platelets. Similarly, the intracellular production of TF in neutrophils triggered by IRA plasma is not hindered by Ticagrelor. Furthermore, DES induce NETs and synchronous stimulation with IRA plasma leads to the formation of thrombogenic TF-bearing NETs. Ticagrelor inhibits stent-induced NET release. These findings suggest a novel immune-modulatory effect of Ticagrelor when it attenuates the formation of thrombogenic NETs. |
| first_indexed | 2024-03-10T19:41:28Z |
| format | Article |
| id | doaj.art-1d2072b8fd3e4dca8261db528171ecf5 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T19:41:28Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-1d2072b8fd3e4dca8261db528171ecf52023-11-20T01:10:30ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-05-012110362510.3390/ijms21103625Ticagrelor Exerts Immune-Modulatory Effect by Attenuating Neutrophil Extracellular TrapsAlexandros Mitsios0Akrivi Chrysanthopoulou1Athanasios Arampatzioglou2Iliana Angelidou3Veroniki Vidali4Konstantinos Ritis5Panagiotis Skendros6Dimitrios Stakos7Laboratory of Molecular Hematology, Department of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, GreeceLaboratory of Molecular Hematology, Department of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, GreeceLaboratory of Molecular Hematology, Department of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, GreeceLaboratory of Molecular Hematology, Department of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, GreeceNatural Products Synthesis and Bioorganic Chemistry Laboratory, Institute of Nanoscience and Nanotechnology, NCSR “Demokritos”, 15310 Athens, GreeceLaboratory of Molecular Hematology, Department of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, GreeceLaboratory of Molecular Hematology, Department of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, GreeceLaboratory of Molecular Hematology, Department of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, GreeceNeutrophils through the release of neutrophil extracellular traps (NETs) containing active tissue factor (TF) are key components of thrombo-inflammation. Platelets-neutrophils interplay in ST elevation myocardial infarction (STEMI) promotes NET formation via inorganic polyphosphates (polyP) released by thrombin-activated platelets. NETs, however, are also induced by biomaterials in a platelet-independent manner. Considering the possible pleiotropic effects of Ticagrelor beyond platelet inhibition and the clinical need for novel antithrombotic strategies targeting inflammation, we investigated the effects of Ticagrelor on polyP and stent-induced NETs in STEMI. Neutrophils from healthy individuals and patients receiving Ticagrelor were stimulated with polyP or drug-eluting stents (DES) to produce NETs. To induce TF expression, neutrophils were further incubated with plasma obtained from the infarct-related artery (IRA) of STEMI patients. The effects of Ticagrelor on NETs and TF loading were assessed using fluorescence microscopy, flow cytometry, myeloperoxidase(MPO)/DNA complex ELISA, and a Western blot. Ticagrelor interrupts platelet–neutrophil interaction by attenuating NETs induced by polyP. However, Ticagrelor does not affect polyP secretion from thrombin-activated platelets. Similarly, the intracellular production of TF in neutrophils triggered by IRA plasma is not hindered by Ticagrelor. Furthermore, DES induce NETs and synchronous stimulation with IRA plasma leads to the formation of thrombogenic TF-bearing NETs. Ticagrelor inhibits stent-induced NET release. These findings suggest a novel immune-modulatory effect of Ticagrelor when it attenuates the formation of thrombogenic NETs.https://www.mdpi.com/1422-0067/21/10/3625neutrophilneutrophil extracellular trapsinorganic polyphosphatethrombo-inflammationticagrelormyocardial infraction |
| spellingShingle | Alexandros Mitsios Akrivi Chrysanthopoulou Athanasios Arampatzioglou Iliana Angelidou Veroniki Vidali Konstantinos Ritis Panagiotis Skendros Dimitrios Stakos Ticagrelor Exerts Immune-Modulatory Effect by Attenuating Neutrophil Extracellular Traps International Journal of Molecular Sciences neutrophil neutrophil extracellular traps inorganic polyphosphate thrombo-inflammation ticagrelor myocardial infraction |
| title | Ticagrelor Exerts Immune-Modulatory Effect by Attenuating Neutrophil Extracellular Traps |
| title_full | Ticagrelor Exerts Immune-Modulatory Effect by Attenuating Neutrophil Extracellular Traps |
| title_fullStr | Ticagrelor Exerts Immune-Modulatory Effect by Attenuating Neutrophil Extracellular Traps |
| title_full_unstemmed | Ticagrelor Exerts Immune-Modulatory Effect by Attenuating Neutrophil Extracellular Traps |
| title_short | Ticagrelor Exerts Immune-Modulatory Effect by Attenuating Neutrophil Extracellular Traps |
| title_sort | ticagrelor exerts immune modulatory effect by attenuating neutrophil extracellular traps |
| topic | neutrophil neutrophil extracellular traps inorganic polyphosphate thrombo-inflammation ticagrelor myocardial infraction |
| url | https://www.mdpi.com/1422-0067/21/10/3625 |
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