Astrocytes Modify Migration of PBMCs Induced by β-Amyloid in a Blood-Brain Barrier in vitro Model
BackgroundThe brain is protected by the blood-brain barrier (BBB), constituted by endothelial cells supported by pericytes and astrocytes. In Alzheimer’s disease a dysregulation of the BBB occurs since the early phases of the disease leading to an increased access of solutes and immune cells that ca...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-07-01
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| Series: | Frontiers in Cellular Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fncel.2019.00337/full |
| _version_ | 1811325975728750592 |
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| author | Simona Federica Spampinato Sara Merlo Evelina Fagone Mary Fruciano Cristina Barbagallo Takashi Kanda Yasuteru Sano Michele Purrello Carlo Vancheri Marco Ragusa Marco Ragusa Maria Angela Sortino |
| author_facet | Simona Federica Spampinato Sara Merlo Evelina Fagone Mary Fruciano Cristina Barbagallo Takashi Kanda Yasuteru Sano Michele Purrello Carlo Vancheri Marco Ragusa Marco Ragusa Maria Angela Sortino |
| author_sort | Simona Federica Spampinato |
| collection | DOAJ |
| description | BackgroundThe brain is protected by the blood-brain barrier (BBB), constituted by endothelial cells supported by pericytes and astrocytes. In Alzheimer’s disease a dysregulation of the BBB occurs since the early phases of the disease leading to an increased access of solutes and immune cells that can participate to the central inflammatory response. Here we investigated whether astrocytes may influence endothelial-leukocytes interaction in the presence of amyloid-β (Aβ).MethodsWe used an in vitro BBB model, where endothelial cells, cultured alone or with astrocytes were exposed for 5 h to Aβ, both under resting or inflammatory conditions (TNFα and IFNγ), to evaluate endothelial barrier properties, as well as transendothelial migration of peripheral blood mononuclear cells (PBMCs).ResultsIn the co-culture model, barrier permeability to solutes was increased by all treatments, but migration was only observed in inflammatory conditions and was prevented by Aβ treatment. On the contrary, in endothelial monocultures, Aβ induced leukocytes migration under resting conditions and did not modify that induced by inflammatory cytokines. In endothelial astrocyte co-cultures, a low molecular weight (MW) isoform of the adhesion molecule ICAM-1, important to allow interaction with PBMCs, was increased after 5 h exposure to inflammatory cytokines, an effect that was prevented by Aβ. This modulation by Aβ was not observed in endothelial monocultures. In addition, endothelial expression of β-1,4-N-acetylglucosaminyltransferase III (Gnt-III), responsible for the formation of the low MW ICAM-1 isoform, was enhanced in inflammatory conditions, but negatively modulated by Aβ only in the co-culture model. miR-200b, increased in astrocytes following Aβ treatment and may represent one of the factors involved in the control of Gnt-III expression.ConclusionThese data point out that, at least in the early phases of Aβ exposure, astrocytes play a role in the modulation of leukocytes migration through the endothelial layer. |
| first_indexed | 2024-04-13T14:42:16Z |
| format | Article |
| id | doaj.art-2ae6a18f2e964304bc73094274d26a68 |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-04-13T14:42:16Z |
| publishDate | 2019-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-2ae6a18f2e964304bc73094274d26a682022-12-22T02:42:52ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022019-07-011310.3389/fncel.2019.00337470716Astrocytes Modify Migration of PBMCs Induced by β-Amyloid in a Blood-Brain Barrier in vitro ModelSimona Federica Spampinato0Sara Merlo1Evelina Fagone2Mary Fruciano3Cristina Barbagallo4Takashi Kanda5Yasuteru Sano6Michele Purrello7Carlo Vancheri8Marco Ragusa9Marco Ragusa10Maria Angela Sortino11Section of Pharmacology, Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, ItalySection of Pharmacology, Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, ItalyDepartment of Clinical and Experimental Medicine, University of Catania, Catania, ItalyDepartment of Clinical and Experimental Medicine, University of Catania, Catania, ItalySection of Biology and Genetics, Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, ItalyDepartment of Neurology and Clinical Neuroscience, Yamaguchi University, Yamaguchi, JapanDepartment of Neurology and Clinical Neuroscience, Yamaguchi University, Yamaguchi, JapanSection of Biology and Genetics, Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, ItalyDepartment of Clinical and Experimental Medicine, University of Catania, Catania, ItalySection of Biology and Genetics, Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, ItalyOasi Research Institute – IRCCS, Troina, ItalySection of Pharmacology, Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, ItalyBackgroundThe brain is protected by the blood-brain barrier (BBB), constituted by endothelial cells supported by pericytes and astrocytes. In Alzheimer’s disease a dysregulation of the BBB occurs since the early phases of the disease leading to an increased access of solutes and immune cells that can participate to the central inflammatory response. Here we investigated whether astrocytes may influence endothelial-leukocytes interaction in the presence of amyloid-β (Aβ).MethodsWe used an in vitro BBB model, where endothelial cells, cultured alone or with astrocytes were exposed for 5 h to Aβ, both under resting or inflammatory conditions (TNFα and IFNγ), to evaluate endothelial barrier properties, as well as transendothelial migration of peripheral blood mononuclear cells (PBMCs).ResultsIn the co-culture model, barrier permeability to solutes was increased by all treatments, but migration was only observed in inflammatory conditions and was prevented by Aβ treatment. On the contrary, in endothelial monocultures, Aβ induced leukocytes migration under resting conditions and did not modify that induced by inflammatory cytokines. In endothelial astrocyte co-cultures, a low molecular weight (MW) isoform of the adhesion molecule ICAM-1, important to allow interaction with PBMCs, was increased after 5 h exposure to inflammatory cytokines, an effect that was prevented by Aβ. This modulation by Aβ was not observed in endothelial monocultures. In addition, endothelial expression of β-1,4-N-acetylglucosaminyltransferase III (Gnt-III), responsible for the formation of the low MW ICAM-1 isoform, was enhanced in inflammatory conditions, but negatively modulated by Aβ only in the co-culture model. miR-200b, increased in astrocytes following Aβ treatment and may represent one of the factors involved in the control of Gnt-III expression.ConclusionThese data point out that, at least in the early phases of Aβ exposure, astrocytes play a role in the modulation of leukocytes migration through the endothelial layer.https://www.frontiersin.org/article/10.3389/fncel.2019.00337/fullAlzheimer’s diseaseendothelial cellscytokinesleukocytesICAM-1VE-cadherin |
| spellingShingle | Simona Federica Spampinato Sara Merlo Evelina Fagone Mary Fruciano Cristina Barbagallo Takashi Kanda Yasuteru Sano Michele Purrello Carlo Vancheri Marco Ragusa Marco Ragusa Maria Angela Sortino Astrocytes Modify Migration of PBMCs Induced by β-Amyloid in a Blood-Brain Barrier in vitro Model Frontiers in Cellular Neuroscience Alzheimer’s disease endothelial cells cytokines leukocytes ICAM-1 VE-cadherin |
| title | Astrocytes Modify Migration of PBMCs Induced by β-Amyloid in a Blood-Brain Barrier in vitro Model |
| title_full | Astrocytes Modify Migration of PBMCs Induced by β-Amyloid in a Blood-Brain Barrier in vitro Model |
| title_fullStr | Astrocytes Modify Migration of PBMCs Induced by β-Amyloid in a Blood-Brain Barrier in vitro Model |
| title_full_unstemmed | Astrocytes Modify Migration of PBMCs Induced by β-Amyloid in a Blood-Brain Barrier in vitro Model |
| title_short | Astrocytes Modify Migration of PBMCs Induced by β-Amyloid in a Blood-Brain Barrier in vitro Model |
| title_sort | astrocytes modify migration of pbmcs induced by β amyloid in a blood brain barrier in vitro model |
| topic | Alzheimer’s disease endothelial cells cytokines leukocytes ICAM-1 VE-cadherin |
| url | https://www.frontiersin.org/article/10.3389/fncel.2019.00337/full |
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