Brain endothelial cell expression of SPARCL-1 is specific to chronic multiple sclerosis lesions and is regulated by inflammatory mediators in vitro.

Autor: Bridel C; Department of Clinical Chemistry, Neurochemistry Lab and Biobank, VU Medical Centre, Amsterdam, The Netherlands., Koel-Simmelink MJA; Department of Clinical Chemistry, Neurochemistry Lab and Biobank, VU Medical Centre, Amsterdam, The Netherlands., Peferoen L; Department of Pathology, VU Medical Centre, Amsterdam, The Netherlands., Derada Troletti C; Department of Molecular Cell Biology and Immunology, Neuroscience Campus Amsterdam, VU University Medical Centre, Amsterdam, The Netherlands., Durieux S; Department of Clinical Chemistry, Neurochemistry Lab and Biobank, VU Medical Centre, Amsterdam, The Netherlands., Gorter R; Department of Pathology, VU Medical Centre, Amsterdam, The Netherlands., Nutma E; Department of Pathology, VU Medical Centre, Amsterdam, The Netherlands., Gami P; Department of Pathology, VU Medical Centre, Amsterdam, The Netherlands., Iacobaeus E; Department of Clinical Neuroscience, Neuroimmunology Unit, Karolinska Institute, Solna, Sweden.; Center for Molecular Medicine, Stockholm, Sweden., Brundin L; Department of Clinical Neuroscience, Neuroimmunology Unit, Karolinska Institute, Solna, Sweden.; Center for Molecular Medicine, Stockholm, Sweden., Kuhle J; Neurology, Department of Medicine, Biomedicine and Clinical Research, University Hospital Basel, Basel, Switzerland., Vrenken H; Department of Radiology and Nuclear Medicine and Department of Physics and Medical Technology, VU University Medical Center, Amsterdam, The Netherlands., Killestein J; Department of Neurology, MS Centre Amsterdam, VU Medical Centre, Amsterdam, The Netherlands., Piersma SR; Department of Medical Oncology, OncoProteomics Laboratory, VU Medical Centre, Amsterdam, The Netherlands., Pham TV; Department of Medical Oncology, OncoProteomics Laboratory, VU Medical Centre, Amsterdam, The Netherlands., De Vries HE; Department of Molecular Cell Biology and Immunology, Neuroscience Campus Amsterdam, VU University Medical Centre, Amsterdam, The Netherlands., Amor S; Department of Pathology, VU Medical Centre, Amsterdam, The Netherlands.; Queen Mary University of London, Blizard Institute, Barts and The London School of Medicine and Dentistry, London, UK., Jimenez CR; Department of Medical Oncology, OncoProteomics Laboratory, VU Medical Centre, Amsterdam, The Netherlands., Teunissen CE; Department of Clinical Chemistry, Neurochemistry Lab and Biobank, VU Medical Centre, Amsterdam, The Netherlands.
Jazyk: angličtina
Zdroj: Neuropathology and applied neurobiology [Neuropathol Appl Neurobiol] 2018 Jun; Vol. 44 (4), pp. 404-416. Date of Electronic Publication: 2017 Jun 28.
DOI: 10.1111/nan.12412
Abstrakt: Aims: Cell matrix modulating protein SPARCL-1 is highly expressed by astrocytes during CNS development and following acute CNS damage. Applying NanoLC-MS/MS to CSF of RRMS and SPMS patients, we identified SPARCL-1 as differentially expressed between these two stages of MS, suggesting a potential as CSF biomarker to differentiate RRMS from SPMS and a role in MS pathogenesis.
Methods: This study examines the potential of SPARCL-1 as CSF biomarker discriminating RRMS from SPMS in three independent cohorts (n = 249), analyses its expression pattern in MS lesions (n = 26), and studies its regulation in cultured human brain microvasculature endothelial cells (BEC) after exposure to MS-relevant inflammatory mediators.
Results: SPARCL-1 expression in CSF was significantly higher in SPMS compared to RRMS in a Dutch cohort of 76 patients. This finding was not replicated in 2 additional cohorts of MS patients from Sweden (n = 81) and Switzerland (n = 92). In chronic MS lesions, but not active lesions or NAWM, a vessel expression pattern of SPARCL-1 was observed in addition to the expression by astrocytes. EC were found to express SPARCL-1 in chronic MS lesions, and SPARCL-1 expression was regulated by MS-relevant inflammatory mediators in cultured human BEC.
Conclusions: Conflicting results of SPARCL-1's differential expression in CSF of three independent cohorts of RRMS and SPMS patients precludes its use as biomarker for disease progression. The expression of SPARCL-1 by BEC in chronic MS lesions together with its regulation by inflammatory mediators in vitro suggest a role for SPARCL-1 in MS neuropathology, possibly at the brain vascular level.
(© 2017 British Neuropathological Society.)
Databáze: MEDLINE
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