The role of plasminogen activator inhibitor-2 in pneumococcal meningitis.


Journal

Acta neuropathologica communications
ISSN: 2051-5960
Titre abrégé: Acta Neuropathol Commun
Pays: England
ID NLM: 101610673

Informations de publication

Date de publication:
29 10 2022
Historique:
received: 07 09 2022
accepted: 12 10 2022
entrez: 30 10 2022
pubmed: 31 10 2022
medline: 2 11 2022
Statut: epublish

Résumé

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

Identifiants

pubmed: 36309755
doi: 10.1186/s40478-022-01461-1
pii: 10.1186/s40478-022-01461-1
pmc: PMC9617400
doi:

Substances chimiques

Plasminogen Activator Inhibitor 2 0
Interleukin-10 130068-27-8
RNA, Messenger 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

155

Informations de copyright

© 2022. The Author(s).

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Auteurs

Nina C Teske (NC)

Laboratory of Neuroinfectious Diseases, Department of Neurology, Klinikum Großhadern, Ludwig-Maximilians University, Munich, Germany.
Department of Neurology, Amsterdam UMC, University of Amsterdam, Amsterdam Neuroscience, PO Box 22660, 1100 DD, Amsterdam, The Netherlands.
European Society for Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Infections of the Brain (ESGIB), Basel, Switzerland.

Joo-Yeon Engelen-Lee (JY)

Department of Neurology, Amsterdam UMC, University of Amsterdam, Amsterdam Neuroscience, PO Box 22660, 1100 DD, Amsterdam, The Netherlands.
European Society for Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Infections of the Brain (ESGIB), Basel, Switzerland.

Susanne Dyckhoff-Shen (S)

Laboratory of Neuroinfectious Diseases, Department of Neurology, Klinikum Großhadern, Ludwig-Maximilians University, Munich, Germany.

Hans-Walter Pfister (HW)

Laboratory of Neuroinfectious Diseases, Department of Neurology, Klinikum Großhadern, Ludwig-Maximilians University, Munich, Germany.

Matthias Klein (M)

Laboratory of Neuroinfectious Diseases, Department of Neurology, Klinikum Großhadern, Ludwig-Maximilians University, Munich, Germany.
European Society for Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Infections of the Brain (ESGIB), Basel, Switzerland.

Diederik van de Beek (D)

Department of Neurology, Amsterdam UMC, University of Amsterdam, Amsterdam Neuroscience, PO Box 22660, 1100 DD, Amsterdam, The Netherlands.
European Society for Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Infections of the Brain (ESGIB), Basel, Switzerland.

Carsten K Kirschning (CK)

Institute of Medical Microbiology, University of Duisburg-Essen, Essen, Germany.

Uwe Koedel (U)

Laboratory of Neuroinfectious Diseases, Department of Neurology, Klinikum Großhadern, Ludwig-Maximilians University, Munich, Germany.
European Society for Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Infections of the Brain (ESGIB), Basel, Switzerland.

Matthijs C Brouwer (MC)

Department of Neurology, Amsterdam UMC, University of Amsterdam, Amsterdam Neuroscience, PO Box 22660, 1100 DD, Amsterdam, The Netherlands. m.c.brouwer@amsterdamumc.nl.
European Society for Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Infections of the Brain (ESGIB), Basel, Switzerland. m.c.brouwer@amsterdamumc.nl.

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