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Plasminogen in cerebrospinal fluid originates from circulating blood
BACKGROUND: Plasminogen activation is a ubiquitous source of fibrinolytic and proteolytic activity. Besides its role in prevention of thrombosis, plasminogen is involved in inflammatory reactions in the central nervous system. Plasminogen has been detected in the cerebrospinal fluid (CSF) of patient...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4173110/ https://www.ncbi.nlm.nih.gov/pubmed/25220760 http://dx.doi.org/10.1186/s12974-014-0154-y |
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author | Mezzapesa, Anna Orset, Cyrille Plawinski, Laurent Doeuvre, Loic Martinez de Lizarrondo, Sara Chimienti, Guglielmina Vivien, Denis Mansour, Alexandre Matà, Sabrina Pepe, Gabriella Anglés-Cano, Eduardo |
author_facet | Mezzapesa, Anna Orset, Cyrille Plawinski, Laurent Doeuvre, Loic Martinez de Lizarrondo, Sara Chimienti, Guglielmina Vivien, Denis Mansour, Alexandre Matà, Sabrina Pepe, Gabriella Anglés-Cano, Eduardo |
author_sort | Mezzapesa, Anna |
collection | PubMed |
description | BACKGROUND: Plasminogen activation is a ubiquitous source of fibrinolytic and proteolytic activity. Besides its role in prevention of thrombosis, plasminogen is involved in inflammatory reactions in the central nervous system. Plasminogen has been detected in the cerebrospinal fluid (CSF) of patients with inflammatory diseases; however, its origin remains controversial, as the blood–CSF barrier may restrict its diffusion from blood. METHODS: We investigated the origin of plasminogen in CSF using Alexa Fluor 488–labelled rat plasminogen injected into rats with systemic inflammation and blood–CSF barrier dysfunction provoked by lipopolysaccharide (LPS). Near-infrared fluorescence imaging and immunohistochemistry fluorescence microscopy were used to identify plasminogen in brain structures, its concentration and functionality were determined by Western blotting and a chromogenic substrate assay, respectively. In parallel, plasminogen was investigated in CSF from patients with Guillain-Barré syndrome (n = 15), multiple sclerosis (n = 19) and noninflammatory neurological diseases (n = 8). RESULTS: Endogenous rat plasminogen was detected in higher amounts in the CSF and urine of LPS-treated animals as compared to controls. In LPS-primed rats, circulating Alexa Fluor 488–labelled rat plasminogen was abundantly localized in the choroid plexus, CSF and urine. Plasminogen in human CSF was higher in Guillain-Barré syndrome (median = 1.28 ng/μl (interquartile range (IQR) = 0.66 to 1.59)) as compared to multiple sclerosis (median = 0.3 ng/μl (IQR = 0.16 to 0.61)) and to noninflammatory neurological diseases (median = 0.27 ng/μl (IQR = 0.18 to 0.35)). CONCLUSIONS: Our findings demonstrate that plasminogen is transported from circulating blood into the CSF of rats via the choroid plexus during inflammation. Our data suggest that a similar mechanism may explain the high CSF concentrations of plasminogen detected in patients with inflammation-derived CSF barrier impairment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12974-014-0154-y) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4173110 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-41731102014-09-25 Plasminogen in cerebrospinal fluid originates from circulating blood Mezzapesa, Anna Orset, Cyrille Plawinski, Laurent Doeuvre, Loic Martinez de Lizarrondo, Sara Chimienti, Guglielmina Vivien, Denis Mansour, Alexandre Matà, Sabrina Pepe, Gabriella Anglés-Cano, Eduardo J Neuroinflammation Research BACKGROUND: Plasminogen activation is a ubiquitous source of fibrinolytic and proteolytic activity. Besides its role in prevention of thrombosis, plasminogen is involved in inflammatory reactions in the central nervous system. Plasminogen has been detected in the cerebrospinal fluid (CSF) of patients with inflammatory diseases; however, its origin remains controversial, as the blood–CSF barrier may restrict its diffusion from blood. METHODS: We investigated the origin of plasminogen in CSF using Alexa Fluor 488–labelled rat plasminogen injected into rats with systemic inflammation and blood–CSF barrier dysfunction provoked by lipopolysaccharide (LPS). Near-infrared fluorescence imaging and immunohistochemistry fluorescence microscopy were used to identify plasminogen in brain structures, its concentration and functionality were determined by Western blotting and a chromogenic substrate assay, respectively. In parallel, plasminogen was investigated in CSF from patients with Guillain-Barré syndrome (n = 15), multiple sclerosis (n = 19) and noninflammatory neurological diseases (n = 8). RESULTS: Endogenous rat plasminogen was detected in higher amounts in the CSF and urine of LPS-treated animals as compared to controls. In LPS-primed rats, circulating Alexa Fluor 488–labelled rat plasminogen was abundantly localized in the choroid plexus, CSF and urine. Plasminogen in human CSF was higher in Guillain-Barré syndrome (median = 1.28 ng/μl (interquartile range (IQR) = 0.66 to 1.59)) as compared to multiple sclerosis (median = 0.3 ng/μl (IQR = 0.16 to 0.61)) and to noninflammatory neurological diseases (median = 0.27 ng/μl (IQR = 0.18 to 0.35)). CONCLUSIONS: Our findings demonstrate that plasminogen is transported from circulating blood into the CSF of rats via the choroid plexus during inflammation. Our data suggest that a similar mechanism may explain the high CSF concentrations of plasminogen detected in patients with inflammation-derived CSF barrier impairment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12974-014-0154-y) contains supplementary material, which is available to authorized users. BioMed Central 2014-09-16 /pmc/articles/PMC4173110/ /pubmed/25220760 http://dx.doi.org/10.1186/s12974-014-0154-y Text en © Mezzapesa et al.; licensee BioMed Central Ltd. 2014 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Mezzapesa, Anna Orset, Cyrille Plawinski, Laurent Doeuvre, Loic Martinez de Lizarrondo, Sara Chimienti, Guglielmina Vivien, Denis Mansour, Alexandre Matà, Sabrina Pepe, Gabriella Anglés-Cano, Eduardo Plasminogen in cerebrospinal fluid originates from circulating blood |
title | Plasminogen in cerebrospinal fluid originates from circulating blood |
title_full | Plasminogen in cerebrospinal fluid originates from circulating blood |
title_fullStr | Plasminogen in cerebrospinal fluid originates from circulating blood |
title_full_unstemmed | Plasminogen in cerebrospinal fluid originates from circulating blood |
title_short | Plasminogen in cerebrospinal fluid originates from circulating blood |
title_sort | plasminogen in cerebrospinal fluid originates from circulating blood |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4173110/ https://www.ncbi.nlm.nih.gov/pubmed/25220760 http://dx.doi.org/10.1186/s12974-014-0154-y |
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