Brain Endothelial Cells Release Apical and Basolateral Microparticles in Response to Inflammatory Cytokine Stimulation: Relevance to Neuroinflammatory Stress?
Microparticles (MP) are regarded both as biomarkers and mediators of many forms of pathology, including neurovascular inflammation. Here, we characterized vectorial release of apical and basolateral MPs (AMPs and BMPs) from control and TNF-α/IFN-γ treated human brain endothelial monolayers, studied...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.01455/full |
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| author | J. Winny Yun Mansoureh Barzegar Christen J. Boyer Alireza Minagar Pierre-Olivier Couraud Jonathan Steven Alexander Jonathan Steven Alexander |
| author_facet | J. Winny Yun Mansoureh Barzegar Christen J. Boyer Alireza Minagar Pierre-Olivier Couraud Jonathan Steven Alexander Jonathan Steven Alexander |
| author_sort | J. Winny Yun |
| collection | DOAJ |
| description | Microparticles (MP) are regarded both as biomarkers and mediators of many forms of pathology, including neurovascular inflammation. Here, we characterized vectorial release of apical and basolateral MPs (AMPs and BMPs) from control and TNF-α/IFN-γ treated human brain endothelial monolayers, studied molecular composition of AMPs and BMPs and characterized molecular pathways regulating AMP and BMP release. The effects of AMPs and BMPs on blood-brain barrier properties and human brain microvascular smooth muscle tonic contractility in vitro were also evaluated. We report that human brain microvascular endothelial cells release MPs both apically and basolaterally with both AMP and BMP release significantly increased following inflammatory cytokine challenge (3.5-fold and 3.9-fold vs. control, respectively). AMPs and BMPs both carry proteins derived from parent cells including those in BBB junctions (Claudin−1, −3, −5, occludin, VE-cadherin). AMPs and BMPs represent distinct populations whose release appears to be regulated by distinctly separate molecular pathways, which depend on signaling from Rho-associated, coiled-coil containing protein kinase (ROCK), calpain as well as cholesterol depletion. AMPs and BMPs modulate functions of neighboring cells including BBB endothelial solute permeability and brain vascular smooth muscle contractility. While control AMPs enhanced brain endothelial barrier, cytokine-induced AMPs impaired BBB. Cytokine-induced but not control BMPs significantly impaired human brain smooth muscle contractility as early as day 1. Taken together these results indicate that AMPs and BMPs may contribute to neurovascular inflammatory disease progression both within the circulation (AMP) and in the brain parenchyma (BMP). |
| first_indexed | 2024-12-11T07:51:03Z |
| format | Article |
| id | doaj.art-db57e76a5ae24ec5a40ecb303f99f862 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-11T07:51:03Z |
| publishDate | 2019-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-db57e76a5ae24ec5a40ecb303f99f8622022-12-22T01:15:20ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-06-011010.3389/fimmu.2019.01455459666Brain Endothelial Cells Release Apical and Basolateral Microparticles in Response to Inflammatory Cytokine Stimulation: Relevance to Neuroinflammatory Stress?J. Winny Yun0Mansoureh Barzegar1Christen J. Boyer2Alireza Minagar3Pierre-Olivier Couraud4Jonathan Steven Alexander5Jonathan Steven Alexander6Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA, United StatesDepartment of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA, United StatesDepartment of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA, United StatesDepartment of Neurology, Louisiana State University Health Sciences Center, Shreveport, LA, United StatesCNRS UMR8104, Institut Cochin, INSERM U1016, Université Paris Descartes, Paris, FranceDepartment of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA, United StatesDepartment of Neurology, Louisiana State University Health Sciences Center, Shreveport, LA, United StatesMicroparticles (MP) are regarded both as biomarkers and mediators of many forms of pathology, including neurovascular inflammation. Here, we characterized vectorial release of apical and basolateral MPs (AMPs and BMPs) from control and TNF-α/IFN-γ treated human brain endothelial monolayers, studied molecular composition of AMPs and BMPs and characterized molecular pathways regulating AMP and BMP release. The effects of AMPs and BMPs on blood-brain barrier properties and human brain microvascular smooth muscle tonic contractility in vitro were also evaluated. We report that human brain microvascular endothelial cells release MPs both apically and basolaterally with both AMP and BMP release significantly increased following inflammatory cytokine challenge (3.5-fold and 3.9-fold vs. control, respectively). AMPs and BMPs both carry proteins derived from parent cells including those in BBB junctions (Claudin−1, −3, −5, occludin, VE-cadherin). AMPs and BMPs represent distinct populations whose release appears to be regulated by distinctly separate molecular pathways, which depend on signaling from Rho-associated, coiled-coil containing protein kinase (ROCK), calpain as well as cholesterol depletion. AMPs and BMPs modulate functions of neighboring cells including BBB endothelial solute permeability and brain vascular smooth muscle contractility. While control AMPs enhanced brain endothelial barrier, cytokine-induced AMPs impaired BBB. Cytokine-induced but not control BMPs significantly impaired human brain smooth muscle contractility as early as day 1. Taken together these results indicate that AMPs and BMPs may contribute to neurovascular inflammatory disease progression both within the circulation (AMP) and in the brain parenchyma (BMP).https://www.frontiersin.org/article/10.3389/fimmu.2019.01455/fullinflammationneurovascularmicroparticleextracellular vesiclebrainendothelial |
| spellingShingle | J. Winny Yun Mansoureh Barzegar Christen J. Boyer Alireza Minagar Pierre-Olivier Couraud Jonathan Steven Alexander Jonathan Steven Alexander Brain Endothelial Cells Release Apical and Basolateral Microparticles in Response to Inflammatory Cytokine Stimulation: Relevance to Neuroinflammatory Stress? Frontiers in Immunology inflammation neurovascular microparticle extracellular vesicle brain endothelial |
| title | Brain Endothelial Cells Release Apical and Basolateral Microparticles in Response to Inflammatory Cytokine Stimulation: Relevance to Neuroinflammatory Stress? |
| title_full | Brain Endothelial Cells Release Apical and Basolateral Microparticles in Response to Inflammatory Cytokine Stimulation: Relevance to Neuroinflammatory Stress? |
| title_fullStr | Brain Endothelial Cells Release Apical and Basolateral Microparticles in Response to Inflammatory Cytokine Stimulation: Relevance to Neuroinflammatory Stress? |
| title_full_unstemmed | Brain Endothelial Cells Release Apical and Basolateral Microparticles in Response to Inflammatory Cytokine Stimulation: Relevance to Neuroinflammatory Stress? |
| title_short | Brain Endothelial Cells Release Apical and Basolateral Microparticles in Response to Inflammatory Cytokine Stimulation: Relevance to Neuroinflammatory Stress? |
| title_sort | brain endothelial cells release apical and basolateral microparticles in response to inflammatory cytokine stimulation relevance to neuroinflammatory stress |
| topic | inflammation neurovascular microparticle extracellular vesicle brain endothelial |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.01455/full |
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