Astrocyte-derived microparticles initiate a neuroinflammatory cycle due to carbon monoxide poisoning

We hypothesized that carbon monoxide (CO) establishes an inflammatory cycle mediated by microparticles (MPs). Mice exposed to a CO protocol (1000 ppm for 40 min and then 3000 ppm for 20 min) that causes neuroinflammation exhibit NF-κB activation in astrocytes leading to generation of MPs express...

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Autores principales:	Deepa Ruhela, Veena M. Bhopale, Sudhakar Kalakonda, Stephen R. Thom
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Astrocyte Thrombospondin-1 Neutrophil Myeloperoxidase CD36 Glymphatics Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/397fe3049e9647c0b961d32e291ebb82
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spelling	oai:doaj.org-article:397fe3049e9647c0b961d32e291ebb822021-12-02T05:03:44ZAstrocyte-derived microparticles initiate a neuroinflammatory cycle due to carbon monoxide poisoning2666-354610.1016/j.bbih.2021.100398https://doaj.org/article/397fe3049e9647c0b961d32e291ebb822021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2666354621002015https://doaj.org/toc/2666-3546We hypothesized that carbon monoxide (CO) establishes an inflammatory cycle mediated by microparticles (MPs). Mice exposed to a CO protocol (1000 ppm for 40 min and then 3000 ppm for 20 min) that causes neuroinflammation exhibit NF-κB activation in astrocytes leading to generation of MPs expressing thrombospondin-1(TSP-1) that collect in deep cervical lymph nodes draining the brain glymphatic system. TSP-1 bearing MPs gain access to the blood stream where they activate neutrophils to generate a new family of MPs, and also stimulate endothelial cells as documented by leakage of intravenous 2000 kDa dextran. At the brain microvasculature, neutrophil and MPs sequestration, and myeloperoxidase activity result in elevations of the p65 subunit of NF-κB, serine 536 phosphorylated p65, CD36, and loss of astrocyte aquaporin-4 that persist for at least 7 days. Knock-out mice lacking the CD36 membrane receptor are resistant to all CO inflammatory changes. Events triggered by CO are recapitulated in naïve wild type mice injected with cervical node MPs from CO-exposed mice, but not control mice. All MPs-mediated events are inhibited with a NF-κB inhibitor, a myeloperoxidase inhibitor, or anti-TSP-1 antibodies. We conclude that astrocyte-derived MPs expressing TSP-1 establish a feed-forward neuroinflammatory cycle involving endothelial CD36-to-astrocyte NF-κB crosstalk. As there is currently no treatment for CO-induced neurological sequelae, these findings pose several possible sites for therapeutic interventions.Deepa RuhelaVeena M. BhopaleSudhakar KalakondaStephen R. ThomElsevierarticleAstrocyteThrombospondin-1NeutrophilMyeloperoxidaseCD36GlymphaticsNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENBrain, Behavior, & Immunity - Health, Vol 18, Iss , Pp 100398- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Astrocyte Thrombospondin-1 Neutrophil Myeloperoxidase CD36 Glymphatics Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	Astrocyte Thrombospondin-1 Neutrophil Myeloperoxidase CD36 Glymphatics Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Deepa Ruhela Veena M. Bhopale Sudhakar Kalakonda Stephen R. Thom Astrocyte-derived microparticles initiate a neuroinflammatory cycle due to carbon monoxide poisoning
description	We hypothesized that carbon monoxide (CO) establishes an inflammatory cycle mediated by microparticles (MPs). Mice exposed to a CO protocol (1000 ppm for 40 min and then 3000 ppm for 20 min) that causes neuroinflammation exhibit NF-κB activation in astrocytes leading to generation of MPs expressing thrombospondin-1(TSP-1) that collect in deep cervical lymph nodes draining the brain glymphatic system. TSP-1 bearing MPs gain access to the blood stream where they activate neutrophils to generate a new family of MPs, and also stimulate endothelial cells as documented by leakage of intravenous 2000 kDa dextran. At the brain microvasculature, neutrophil and MPs sequestration, and myeloperoxidase activity result in elevations of the p65 subunit of NF-κB, serine 536 phosphorylated p65, CD36, and loss of astrocyte aquaporin-4 that persist for at least 7 days. Knock-out mice lacking the CD36 membrane receptor are resistant to all CO inflammatory changes. Events triggered by CO are recapitulated in naïve wild type mice injected with cervical node MPs from CO-exposed mice, but not control mice. All MPs-mediated events are inhibited with a NF-κB inhibitor, a myeloperoxidase inhibitor, or anti-TSP-1 antibodies. We conclude that astrocyte-derived MPs expressing TSP-1 establish a feed-forward neuroinflammatory cycle involving endothelial CD36-to-astrocyte NF-κB crosstalk. As there is currently no treatment for CO-induced neurological sequelae, these findings pose several possible sites for therapeutic interventions.
format	article
author	Deepa Ruhela Veena M. Bhopale Sudhakar Kalakonda Stephen R. Thom
author_facet	Deepa Ruhela Veena M. Bhopale Sudhakar Kalakonda Stephen R. Thom
author_sort	Deepa Ruhela
title	Astrocyte-derived microparticles initiate a neuroinflammatory cycle due to carbon monoxide poisoning
title_short	Astrocyte-derived microparticles initiate a neuroinflammatory cycle due to carbon monoxide poisoning
title_full	Astrocyte-derived microparticles initiate a neuroinflammatory cycle due to carbon monoxide poisoning
title_fullStr	Astrocyte-derived microparticles initiate a neuroinflammatory cycle due to carbon monoxide poisoning
title_full_unstemmed	Astrocyte-derived microparticles initiate a neuroinflammatory cycle due to carbon monoxide poisoning
title_sort	astrocyte-derived microparticles initiate a neuroinflammatory cycle due to carbon monoxide poisoning
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/397fe3049e9647c0b961d32e291ebb82
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Astrocyte-derived microparticles initiate a neuroinflammatory cycle due to carbon monoxide poisoning

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