التفاصيل البيبلوغرافية
| العنوان: |
The role of plasminogen activator inhibitor-2 in pneumococcal meningitis |
| المؤلفون: |
Teske, Nina C., Engelen-Lee, Joo-Yeon, Dyckhoff-Shen, Susanne, Pfister, Hans-Walter, Klein, Matthias, van de Beek, Diederik, Kirschning, Carsten K., Koedel, Uwe, Brouwer, Matthijs C. |
| المساهمون: |
European Society of Clinical Microbiology and Infectious Diseases, European Federation of Neurological Sciences, Netherlands Organization for Health Research and Development |
| المصدر: |
Acta Neuropathologica Communications ; volume 10, issue 1 ; ISSN 2051-5960 |
| بيانات النشر: |
Springer Science and Business Media LLC |
| سنة النشر: |
2022 |
| مصطلحات موضوعية: |
Cellular and Molecular Neuroscience, Neurology (clinical), Pathology and Forensic Medicine |
| الوصف: |
Pneumococcal meningitis is associated with dysregulation of the coagulation cascade. Previously, we detected upregulation of cerebral plasminogen activator inhibitor-2 (PAI-2) mRNA expression during pneumococcal meningitis. Diverse functions have been ascribed to PAI-2, but its role remains unclear. We analyzed the function of SERPINB2 (coding for PAI-2) in patients with bacterial meningitis, in a well-established pneumococcal meningitis mouse model, using Serpinb2 knockout mice, and in vitro in wt and PAI-2-deficient bone marrow-derived macrophages (BMDMs). We measured PAI-2 in cerebrospinal fluid of patients, and performed functional, histopathological, protein and mRNA expression analyses in vivo and in vitro. We found a substantial increase of PAI-2 concentration in CSF of patients with pneumococcal meningitis, and up-regulation and increased release of PAI-2 in mice. PAI-2 deficiency was associated with increased mortality in murine pneumococcal meningitis and cerebral hemorrhages. Serpinb2 −/ − mice exhibited increased C5a levels, but decreased IL-10 levels in the brain during pneumococcal infection. Our in vitro experiments confirmed increased expression and release of PAI-2 by wt BMDM and decreased IL-10 liberation by PAI-2-deficient BMDM upon pneumococcal challenge. Our data show that PAI-2 is elevated during in pneumococcal meningitis in humans and mice. PAI-2 deficiency causes an inflammatory imbalance, resulting in increased brain pathology and mortality. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| DOI: |
10.1186/s40478-022-01461-1 |
| DOI: |
10.1186/s40478-022-01461-1.pdf |
| DOI: |
10.1186/s40478-022-01461-1/fulltext.html |
| الإتاحة: |
https://doi.org/10.1186/s40478-022-01461-1Test |
| حقوق: |
https://creativecommons.org/licenses/by/4.0Test ; https://creativecommons.org/licenses/by/4.0Test |
| رقم الانضمام: |
edsbas.B0AE076A |
| قاعدة البيانات: |
BASE |
