Stroke-derived neutrophils demonstrate higher formation potential and impaired resolution of CD66b + driven neutrophil extracellular traps
Abstract Background Recent evidence suggests a merging role of immunothrombosis in the formation of arterial thrombosis. Our study aims to investigate its relevance in stroke patients. Methods We compared the peripheral immunological profile of stroke patients vs. healthy controls. Serum samples wer...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-05-01
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| Series: | BMC Neurology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12883-022-02707-0 |
| _version_ | 1797795654110543872 |
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| author | Angeliki Datsi Laura Piotrowski Markella Markou Thomas Köster Isabelle Kohtz Kerstin Lang Sabine Plöttner Heiko Udo Käfferlein Burkhard Pleger Ramon Martinez Bogdan Pintea Roland Fried Marcus Müller Rene Chapot Konstantinos Gousias |
| author_facet | Angeliki Datsi Laura Piotrowski Markella Markou Thomas Köster Isabelle Kohtz Kerstin Lang Sabine Plöttner Heiko Udo Käfferlein Burkhard Pleger Ramon Martinez Bogdan Pintea Roland Fried Marcus Müller Rene Chapot Konstantinos Gousias |
| author_sort | Angeliki Datsi |
| collection | DOAJ |
| description | Abstract Background Recent evidence suggests a merging role of immunothrombosis in the formation of arterial thrombosis. Our study aims to investigate its relevance in stroke patients. Methods We compared the peripheral immunological profile of stroke patients vs. healthy controls. Serum samples were functionally analyzed for their formation and clearance of Neutrophil-Extracellular-Traps. The composition of retrieved thrombi has been immunologically analyzed. Results Peripheral blood of stroke patients showed significantly elevated levels of DNAse-I (p < 0.001), LDG (p = 0.003), CD4 (p = 0.005) as well as the pro-inflammatory cytokines IL-17 (p < 0.001), INF-γ (p < 0.001) and IL-22 (p < 0.001) compared to controls, reflecting a TH1/TH17 response. Increased counts of DNAse-I in sera (p = 0.045) and Neutrophil-Extracellular-Traps in thrombi (p = 0.032) have been observed in patients with onset time of symptoms longer than 4,5 h. Lower values of CD66b in thrombi were independently associated with greater improvement of NIHSS after mechanical thrombectomy (p = 0.045). Stroke-derived neutrophils show higher potential for Neutrophil-Extracellular-Traps formation after stimulation and worse resolution under DNAse-I treatment compared to neutrophils derived from healthy individuals. Conclusions Our data provide new insight in the role of activated neutrophils and Neutrophil-Extracellular-Traps in ischemic stroke. Future larger studies are warranted to further investigate the role of immunothrombosis in the cascades of stroke. Trial registration DRKS, DRKS00013278, Registered 15 November 2017, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00013278 |
| first_indexed | 2024-03-13T03:21:16Z |
| format | Article |
| id | doaj.art-864d218195f24bbea6950134437c7fc4 |
| institution | Directory Open Access Journal |
| issn | 1471-2377 |
| language | English |
| last_indexed | 2024-03-13T03:21:16Z |
| publishDate | 2022-05-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Neurology |
| spelling | doaj.art-864d218195f24bbea6950134437c7fc42023-06-25T11:20:26ZengBMCBMC Neurology1471-23772022-05-0122111110.1186/s12883-022-02707-0Stroke-derived neutrophils demonstrate higher formation potential and impaired resolution of CD66b + driven neutrophil extracellular trapsAngeliki Datsi0Laura Piotrowski1Markella Markou2Thomas Köster3Isabelle Kohtz4Kerstin Lang5Sabine Plöttner6Heiko Udo Käfferlein7Burkhard Pleger8Ramon Martinez9Bogdan Pintea10Roland Fried11Marcus Müller12Rene Chapot13Konstantinos Gousias14Institute for Transplantation Diagnostics and Cell Therapeutics, Heinrich-Heine-University DüsseldorfMedical School, Rheinische Friedrich-Wilhelms University of BonnDepartment of Neurology and Psychotraumatology, BG Klinikum DuisburgDepartment for Diagnostic and Interventional Radiology, University Hospital Bonn Venusberg-Campus 1Ruhr University BochumInstitute for Prevention and Occupational Medicine (IPA) Ruhr University Bochum (IPA)Institute for Prevention and Occupational Medicine (IPA) Ruhr University Bochum (IPA)Institute for Prevention and Occupational Medicine (IPA) Ruhr University Bochum (IPA)Department of Neurology, University Hospital Bergmannsheil BochumDepartment of BG Neurosurgery and Spinal Surgery, University Hospital Bergmannsheil BochumDepartment of BG Neurosurgery and Spinal Surgery, University Hospital Bergmannsheil BochumStatistics in the Biosciences, TU Dortmund UniversityDepartment of Neurology, St Marien Academic Hospital HammDepartment of Radiology and NeuroradiologyDepartment of Neurosurgery, KLW St Paulus Corporation, St Marien Academic Hospital Lünen, Westfälische Wilhelms-University MünsterAbstract Background Recent evidence suggests a merging role of immunothrombosis in the formation of arterial thrombosis. Our study aims to investigate its relevance in stroke patients. Methods We compared the peripheral immunological profile of stroke patients vs. healthy controls. Serum samples were functionally analyzed for their formation and clearance of Neutrophil-Extracellular-Traps. The composition of retrieved thrombi has been immunologically analyzed. Results Peripheral blood of stroke patients showed significantly elevated levels of DNAse-I (p < 0.001), LDG (p = 0.003), CD4 (p = 0.005) as well as the pro-inflammatory cytokines IL-17 (p < 0.001), INF-γ (p < 0.001) and IL-22 (p < 0.001) compared to controls, reflecting a TH1/TH17 response. Increased counts of DNAse-I in sera (p = 0.045) and Neutrophil-Extracellular-Traps in thrombi (p = 0.032) have been observed in patients with onset time of symptoms longer than 4,5 h. Lower values of CD66b in thrombi were independently associated with greater improvement of NIHSS after mechanical thrombectomy (p = 0.045). Stroke-derived neutrophils show higher potential for Neutrophil-Extracellular-Traps formation after stimulation and worse resolution under DNAse-I treatment compared to neutrophils derived from healthy individuals. Conclusions Our data provide new insight in the role of activated neutrophils and Neutrophil-Extracellular-Traps in ischemic stroke. Future larger studies are warranted to further investigate the role of immunothrombosis in the cascades of stroke. Trial registration DRKS, DRKS00013278, Registered 15 November 2017, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00013278https://doi.org/10.1186/s12883-022-02707-0StrokeThrombusNeutrophil-Extracellular-TrapsCD66b + Immunothrombosis |
| spellingShingle | Angeliki Datsi Laura Piotrowski Markella Markou Thomas Köster Isabelle Kohtz Kerstin Lang Sabine Plöttner Heiko Udo Käfferlein Burkhard Pleger Ramon Martinez Bogdan Pintea Roland Fried Marcus Müller Rene Chapot Konstantinos Gousias Stroke-derived neutrophils demonstrate higher formation potential and impaired resolution of CD66b + driven neutrophil extracellular traps BMC Neurology Stroke Thrombus Neutrophil-Extracellular-Traps CD66b + Immunothrombosis |
| title | Stroke-derived neutrophils demonstrate higher formation potential and impaired resolution of CD66b + driven neutrophil extracellular traps |
| title_full | Stroke-derived neutrophils demonstrate higher formation potential and impaired resolution of CD66b + driven neutrophil extracellular traps |
| title_fullStr | Stroke-derived neutrophils demonstrate higher formation potential and impaired resolution of CD66b + driven neutrophil extracellular traps |
| title_full_unstemmed | Stroke-derived neutrophils demonstrate higher formation potential and impaired resolution of CD66b + driven neutrophil extracellular traps |
| title_short | Stroke-derived neutrophils demonstrate higher formation potential and impaired resolution of CD66b + driven neutrophil extracellular traps |
| title_sort | stroke derived neutrophils demonstrate higher formation potential and impaired resolution of cd66b driven neutrophil extracellular traps |
| topic | Stroke Thrombus Neutrophil-Extracellular-Traps CD66b + Immunothrombosis |
| url | https://doi.org/10.1186/s12883-022-02707-0 |
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