Neutrophils Are Dysregulated in Patients with Hereditary Angioedema Types I and II in a Symptom-Free Period
Neutrophils impact on processes preceding the formation of bradykinin, a major swelling mediator in hereditary angioedema (HAE), yet their potential role in HAE pathogenesis has not been sufficiently studied. We assessed the relative mRNA expression of 10 genes related to neutrophil activation using...
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| Format: | Article |
| Language: | English |
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Wiley
2019-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2019/9515628 |
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| author | Tereza Grymova Marcela Vlkova Premysl Soucek Roman Hakl Jana Nechvatalova Peter Slanina Julie Stichova Jiri Litzman Tomas Freiberger |
| author_facet | Tereza Grymova Marcela Vlkova Premysl Soucek Roman Hakl Jana Nechvatalova Peter Slanina Julie Stichova Jiri Litzman Tomas Freiberger |
| author_sort | Tereza Grymova |
| collection | DOAJ |
| description | Neutrophils impact on processes preceding the formation of bradykinin, a major swelling mediator in hereditary angioedema (HAE), yet their potential role in HAE pathogenesis has not been sufficiently studied. We assessed the relative mRNA expression of 10 genes related to neutrophil activation using RNA extracted from the peripheral blood neutrophils of 23 HAE patients in a symptom-free period and 39 healthy donors. Increased relative mRNA expression levels of CD274, IL1B, IL1RN, IL8, MMP9, and TLR4, together with a lack in their mutual correlations detected in HAE patients compared to healthy controls, suggested a preactivated state and dysregulation of patients’ neutrophils. Patients’ neutrophil-alerted state was further supported by increased CD11b, decreased CD16 plasma membrane deposition, and increased relative CD274+ and CD87+ neutrophil counts, but not by increased neutrophil elastase or myeloperoxidase plasma levels. As CD274 mediates inhibitory signals to different immune cells, neutrophils were cocultured with T-cells/PBMC. The decrease in CD25+ and IFN-γ+ T-cell/PBMC ratio in patients indicated the patients’ neutrophil suppressive functions. In summary, the results showed neutrophils’ alerted state and dysregulation at the transcript level in patients with HAE types I and II even in a symptom-free period, which might make them more susceptible to edema formation. Neutrophils’ T-cell suppressive capacity in HAE patients needs to be further investigated. |
| format | Article |
| id | doaj-art-a2a35a4c26974bf78115c9d22cf318de |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-a2a35a4c26974bf78115c9d22cf318de2025-02-03T01:21:51ZengWileyMediators of Inflammation0962-93511466-18612019-01-01201910.1155/2019/95156289515628Neutrophils Are Dysregulated in Patients with Hereditary Angioedema Types I and II in a Symptom-Free PeriodTereza Grymova0Marcela Vlkova1Premysl Soucek2Roman Hakl3Jana Nechvatalova4Peter Slanina5Julie Stichova6Jiri Litzman7Tomas Freiberger8Centre for Cardiovascular Surgery and Transplantation, Brno, Czech RepublicDepartment of Clinical Immunology and Allergology, Faculty of Medicine, Masaryk University, Brno, Czech RepublicCentre for Cardiovascular Surgery and Transplantation, Brno, Czech RepublicDepartment of Clinical Immunology and Allergology, Faculty of Medicine, Masaryk University, Brno, Czech RepublicDepartment of Clinical Immunology and Allergology, Faculty of Medicine, Masaryk University, Brno, Czech RepublicDepartment of Clinical Immunology and Allergology, Faculty of Medicine, Masaryk University, Brno, Czech RepublicDepartment of Clinical Immunology and Allergology, Faculty of Medicine, Masaryk University, Brno, Czech RepublicDepartment of Clinical Immunology and Allergology, Faculty of Medicine, Masaryk University, Brno, Czech RepublicCentre for Cardiovascular Surgery and Transplantation, Brno, Czech RepublicNeutrophils impact on processes preceding the formation of bradykinin, a major swelling mediator in hereditary angioedema (HAE), yet their potential role in HAE pathogenesis has not been sufficiently studied. We assessed the relative mRNA expression of 10 genes related to neutrophil activation using RNA extracted from the peripheral blood neutrophils of 23 HAE patients in a symptom-free period and 39 healthy donors. Increased relative mRNA expression levels of CD274, IL1B, IL1RN, IL8, MMP9, and TLR4, together with a lack in their mutual correlations detected in HAE patients compared to healthy controls, suggested a preactivated state and dysregulation of patients’ neutrophils. Patients’ neutrophil-alerted state was further supported by increased CD11b, decreased CD16 plasma membrane deposition, and increased relative CD274+ and CD87+ neutrophil counts, but not by increased neutrophil elastase or myeloperoxidase plasma levels. As CD274 mediates inhibitory signals to different immune cells, neutrophils were cocultured with T-cells/PBMC. The decrease in CD25+ and IFN-γ+ T-cell/PBMC ratio in patients indicated the patients’ neutrophil suppressive functions. In summary, the results showed neutrophils’ alerted state and dysregulation at the transcript level in patients with HAE types I and II even in a symptom-free period, which might make them more susceptible to edema formation. Neutrophils’ T-cell suppressive capacity in HAE patients needs to be further investigated.http://dx.doi.org/10.1155/2019/9515628 |
| spellingShingle | Tereza Grymova Marcela Vlkova Premysl Soucek Roman Hakl Jana Nechvatalova Peter Slanina Julie Stichova Jiri Litzman Tomas Freiberger Neutrophils Are Dysregulated in Patients with Hereditary Angioedema Types I and II in a Symptom-Free Period Mediators of Inflammation |
| title | Neutrophils Are Dysregulated in Patients with Hereditary Angioedema Types I and II in a Symptom-Free Period |
| title_full | Neutrophils Are Dysregulated in Patients with Hereditary Angioedema Types I and II in a Symptom-Free Period |
| title_fullStr | Neutrophils Are Dysregulated in Patients with Hereditary Angioedema Types I and II in a Symptom-Free Period |
| title_full_unstemmed | Neutrophils Are Dysregulated in Patients with Hereditary Angioedema Types I and II in a Symptom-Free Period |
| title_short | Neutrophils Are Dysregulated in Patients with Hereditary Angioedema Types I and II in a Symptom-Free Period |
| title_sort | neutrophils are dysregulated in patients with hereditary angioedema types i and ii in a symptom free period |
| url | http://dx.doi.org/10.1155/2019/9515628 |
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