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Plasma VCAM1 levels correlate with disease severity in Parkinson’s disease
BACKGROUND: Parkinson’s disease (PD) is a progressive neurodegenerative disease characterized by motor and non-motor symptoms. There is increasing evidence that PD pathology is accompanied by an inflammatory response. This is highly relevant for understanding disease progression and the development...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6507178/ https://www.ncbi.nlm.nih.gov/pubmed/31068198 http://dx.doi.org/10.1186/s12974-019-1482-8 |
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author | Perner, Caroline Perner, Florian Gaur, Nayana Zimmermann, Silke Witte, Otto W. Heidel, Florian H. Grosskreutz, Julian Prell, Tino |
author_facet | Perner, Caroline Perner, Florian Gaur, Nayana Zimmermann, Silke Witte, Otto W. Heidel, Florian H. Grosskreutz, Julian Prell, Tino |
author_sort | Perner, Caroline |
collection | PubMed |
description | BACKGROUND: Parkinson’s disease (PD) is a progressive neurodegenerative disease characterized by motor and non-motor symptoms. There is increasing evidence that PD pathology is accompanied by an inflammatory response. This is highly relevant for understanding disease progression and the development of novel neuroprotective therapies. OBJECTIVE: Assessing potential dysregulation of a panel of inflammatory mediators in the peripheral blood mononuclear cells (PBMCs) and plasma of PD patients and in the context of clinical outcome metrics. METHODS: We performed a screening of selected cell-surface chemokine receptors and adhesion molecules in PBMCs from PD patients and age-matched healthy controls in a flow cytometry-based assay. ELISA was used to quantify VCAM1 levels in the plasma of PD patients. Lymphocytic chemotactic ability was assessed using a modified Boyden chamber assay. RESULTS: VLA4 expression was significantly downregulated on CD3+ T cells, CD56+ NK cells, and CD3+/CD56+ NK-T cells from PD patients; further, an increase of the soluble VLA4 ligand VCAM1 in patient plasma was noted. sVCAM1 in PD patients was even higher than reported for patients with multiple sclerosis, neuromyelitis optica, and rheumatoid arthritis. sVCAM1 levels correlated with the disease stage (Hoehn and Yahr scale) and motor impairment. Chemoattraction with SDF-1α revealed impaired motility of lymphocytes from PD patients relative to controls. CONCLUSION: Our data provides evidence for a functional dysregulation of the sVCAM1-VLA4 axis in PD. Further studies evaluating the therapeutic potential of this axis are warranted. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12974-019-1482-8) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6507178 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-65071782019-05-13 Plasma VCAM1 levels correlate with disease severity in Parkinson’s disease Perner, Caroline Perner, Florian Gaur, Nayana Zimmermann, Silke Witte, Otto W. Heidel, Florian H. Grosskreutz, Julian Prell, Tino J Neuroinflammation Letter to the Editor BACKGROUND: Parkinson’s disease (PD) is a progressive neurodegenerative disease characterized by motor and non-motor symptoms. There is increasing evidence that PD pathology is accompanied by an inflammatory response. This is highly relevant for understanding disease progression and the development of novel neuroprotective therapies. OBJECTIVE: Assessing potential dysregulation of a panel of inflammatory mediators in the peripheral blood mononuclear cells (PBMCs) and plasma of PD patients and in the context of clinical outcome metrics. METHODS: We performed a screening of selected cell-surface chemokine receptors and adhesion molecules in PBMCs from PD patients and age-matched healthy controls in a flow cytometry-based assay. ELISA was used to quantify VCAM1 levels in the plasma of PD patients. Lymphocytic chemotactic ability was assessed using a modified Boyden chamber assay. RESULTS: VLA4 expression was significantly downregulated on CD3+ T cells, CD56+ NK cells, and CD3+/CD56+ NK-T cells from PD patients; further, an increase of the soluble VLA4 ligand VCAM1 in patient plasma was noted. sVCAM1 in PD patients was even higher than reported for patients with multiple sclerosis, neuromyelitis optica, and rheumatoid arthritis. sVCAM1 levels correlated with the disease stage (Hoehn and Yahr scale) and motor impairment. Chemoattraction with SDF-1α revealed impaired motility of lymphocytes from PD patients relative to controls. CONCLUSION: Our data provides evidence for a functional dysregulation of the sVCAM1-VLA4 axis in PD. Further studies evaluating the therapeutic potential of this axis are warranted. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12974-019-1482-8) contains supplementary material, which is available to authorized users. BioMed Central 2019-05-08 /pmc/articles/PMC6507178/ /pubmed/31068198 http://dx.doi.org/10.1186/s12974-019-1482-8 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. 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 | Letter to the Editor Perner, Caroline Perner, Florian Gaur, Nayana Zimmermann, Silke Witte, Otto W. Heidel, Florian H. Grosskreutz, Julian Prell, Tino Plasma VCAM1 levels correlate with disease severity in Parkinson’s disease |
title | Plasma VCAM1 levels correlate with disease severity in Parkinson’s disease |
title_full | Plasma VCAM1 levels correlate with disease severity in Parkinson’s disease |
title_fullStr | Plasma VCAM1 levels correlate with disease severity in Parkinson’s disease |
title_full_unstemmed | Plasma VCAM1 levels correlate with disease severity in Parkinson’s disease |
title_short | Plasma VCAM1 levels correlate with disease severity in Parkinson’s disease |
title_sort | plasma vcam1 levels correlate with disease severity in parkinson’s disease |
topic | Letter to the Editor |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6507178/ https://www.ncbi.nlm.nih.gov/pubmed/31068198 http://dx.doi.org/10.1186/s12974-019-1482-8 |
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