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Hypothiocyanous Acid Disrupts the Barrier Function of Brain Endothelial Cells

Inflammation is a common feature of neurological diseases. During neuroinflammation, neutrophils are recruited to the brain vasculature, where myeloperoxidase can produce hypochlorous acid and the less well-studied oxidant hypothiocyanous acid (HOSCN). In this study, we exposed primary brain endothe...

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Autores principales: van Leeuwen, Eveline, Hampton, Mark B., Smyth, Leon C. D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9030776/
https://www.ncbi.nlm.nih.gov/pubmed/35453292
http://dx.doi.org/10.3390/antiox11040608
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author van Leeuwen, Eveline
Hampton, Mark B.
Smyth, Leon C. D.
author_facet van Leeuwen, Eveline
Hampton, Mark B.
Smyth, Leon C. D.
author_sort van Leeuwen, Eveline
collection PubMed
description Inflammation is a common feature of neurological diseases. During neuroinflammation, neutrophils are recruited to the brain vasculature, where myeloperoxidase can produce hypochlorous acid and the less well-studied oxidant hypothiocyanous acid (HOSCN). In this study, we exposed primary brain endothelial cells (BECs) to HOSCN and observed a rapid loss of transendothelial electrical resistance (TEER) at sublethal concentrations. Decreased barrier function was associated with a loss of tight junctions at cellular contacts and a concomitant loss of dynamic microtubules. Both tight junction and cytoskeletal disruptions were visible within 30 min of exposure, whereas significant loss of TEER took more than 1 h. The removal of the HOSCN after 30 min prevented subsequent barrier dysfunction. These results indicate that BECs are sensitive to HOSCN, resulting in the eventual loss of barrier function. We hypothesise that this mechanism may be relevant in neutrophil transmigration, with HOSCN facilitating blood–brain barrier opening at the sites of egress. Furthermore, this mechanism may be a way through which neutrophils, residing in the vasculature, can influence neuroinflammation in diseases.
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spelling pubmed-90307762022-04-23 Hypothiocyanous Acid Disrupts the Barrier Function of Brain Endothelial Cells van Leeuwen, Eveline Hampton, Mark B. Smyth, Leon C. D. Antioxidants (Basel) Article Inflammation is a common feature of neurological diseases. During neuroinflammation, neutrophils are recruited to the brain vasculature, where myeloperoxidase can produce hypochlorous acid and the less well-studied oxidant hypothiocyanous acid (HOSCN). In this study, we exposed primary brain endothelial cells (BECs) to HOSCN and observed a rapid loss of transendothelial electrical resistance (TEER) at sublethal concentrations. Decreased barrier function was associated with a loss of tight junctions at cellular contacts and a concomitant loss of dynamic microtubules. Both tight junction and cytoskeletal disruptions were visible within 30 min of exposure, whereas significant loss of TEER took more than 1 h. The removal of the HOSCN after 30 min prevented subsequent barrier dysfunction. These results indicate that BECs are sensitive to HOSCN, resulting in the eventual loss of barrier function. We hypothesise that this mechanism may be relevant in neutrophil transmigration, with HOSCN facilitating blood–brain barrier opening at the sites of egress. Furthermore, this mechanism may be a way through which neutrophils, residing in the vasculature, can influence neuroinflammation in diseases. MDPI 2022-03-22 /pmc/articles/PMC9030776/ /pubmed/35453292 http://dx.doi.org/10.3390/antiox11040608 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
van Leeuwen, Eveline
Hampton, Mark B.
Smyth, Leon C. D.
Hypothiocyanous Acid Disrupts the Barrier Function of Brain Endothelial Cells
title Hypothiocyanous Acid Disrupts the Barrier Function of Brain Endothelial Cells
title_full Hypothiocyanous Acid Disrupts the Barrier Function of Brain Endothelial Cells
title_fullStr Hypothiocyanous Acid Disrupts the Barrier Function of Brain Endothelial Cells
title_full_unstemmed Hypothiocyanous Acid Disrupts the Barrier Function of Brain Endothelial Cells
title_short Hypothiocyanous Acid Disrupts the Barrier Function of Brain Endothelial Cells
title_sort hypothiocyanous acid disrupts the barrier function of brain endothelial cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9030776/
https://www.ncbi.nlm.nih.gov/pubmed/35453292
http://dx.doi.org/10.3390/antiox11040608
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