Brain Endothelial Erythrophagocytosis and Hemoglobin Transmigration Across Brain Endothelium: Implications for Pathogenesis of Cerebral Microbleeds
Peripheral endothelial cells are capable of erythrophagocytosis, but data on brain endothelial erythrophagocytosis are limited. We studied the relationship between brain endothelial erythrophagocytosis and cerebral microhemorrhage, the pathological substrate of MRI-demonstrable cerebral microbleeds....
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| Format: | Article |
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Frontiers Media S.A.
2018-09-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fncel.2018.00279/full |
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| author | Rudy Chang Juan Castillo Alexander C. Zambon Tatiana B. Krasieva Mark J. Fisher Rachita K. Sumbria Rachita K. Sumbria |
| author_facet | Rudy Chang Juan Castillo Alexander C. Zambon Tatiana B. Krasieva Mark J. Fisher Rachita K. Sumbria Rachita K. Sumbria |
| author_sort | Rudy Chang |
| collection | DOAJ |
| description | Peripheral endothelial cells are capable of erythrophagocytosis, but data on brain endothelial erythrophagocytosis are limited. We studied the relationship between brain endothelial erythrophagocytosis and cerebral microhemorrhage, the pathological substrate of MRI-demonstrable cerebral microbleeds. To demonstrate the erythrophagocytic capability of the brain endothelium, we studied the interactions between brain endothelial cells and red blood cells exposed to oxidative stress in vitro, and developed a new in vitro cerebral microbleeds model to study the subsequent passage of hemoglobin across the brain endothelial monolayer. Using multiple approaches, our results show marked brain endothelial erythrophagocytosis of red blood cells exposed to oxidative stress compared with control red blood cells in vitro. This brain endothelial erythrophagocytosis was accompanied by passage of hemoglobin across the brain endothelial monolayer with unaltered monolayer integrity. In vivo and confocal fluorescence microscopy studies confirmed the extravasation of RBC exposed to oxidative stress across brain endothelium. These findings, demonstrating erythrophagocytosis mediated by the brain endothelial monolayer and the subsequent passage of iron-rich hemoglobin in vitro and RBC in vivo, may have implications for elucidating mechanisms involved in the development of cerebral microbleeds that are not dependent on disruption of the microvasculature. |
| first_indexed | 2024-12-13T10:20:29Z |
| format | Article |
| id | doaj.art-bfc0583c94234745863ca774eb85528d |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-12-13T10:20:29Z |
| publishDate | 2018-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-bfc0583c94234745863ca774eb85528d2022-12-21T23:51:13ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022018-09-011210.3389/fncel.2018.00279360414Brain Endothelial Erythrophagocytosis and Hemoglobin Transmigration Across Brain Endothelium: Implications for Pathogenesis of Cerebral MicrobleedsRudy Chang0Juan Castillo1Alexander C. Zambon2Tatiana B. Krasieva3Mark J. Fisher4Rachita K. Sumbria5Rachita K. Sumbria6Department of Biopharmaceutical Sciences, School of Pharmacy and Health Sciences, Keck Graduate Institute, Claremont, CA, United StatesDepartment of Neuroscience, Claremont McKenna College, Claremont, CA, United StatesDepartment of Biopharmaceutical Sciences, School of Pharmacy and Health Sciences, Keck Graduate Institute, Claremont, CA, United StatesBeckman Laser Institute, University of California, Irvine, Irvine, CA, United StatesDepartments of Neurology and Pathology & Laboratory Medicine, University of California, Irvine, Irvine, CA, United StatesDepartment of Biopharmaceutical Sciences, School of Pharmacy and Health Sciences, Keck Graduate Institute, Claremont, CA, United StatesDepartments of Neurology and Pathology & Laboratory Medicine, University of California, Irvine, Irvine, CA, United StatesPeripheral endothelial cells are capable of erythrophagocytosis, but data on brain endothelial erythrophagocytosis are limited. We studied the relationship between brain endothelial erythrophagocytosis and cerebral microhemorrhage, the pathological substrate of MRI-demonstrable cerebral microbleeds. To demonstrate the erythrophagocytic capability of the brain endothelium, we studied the interactions between brain endothelial cells and red blood cells exposed to oxidative stress in vitro, and developed a new in vitro cerebral microbleeds model to study the subsequent passage of hemoglobin across the brain endothelial monolayer. Using multiple approaches, our results show marked brain endothelial erythrophagocytosis of red blood cells exposed to oxidative stress compared with control red blood cells in vitro. This brain endothelial erythrophagocytosis was accompanied by passage of hemoglobin across the brain endothelial monolayer with unaltered monolayer integrity. In vivo and confocal fluorescence microscopy studies confirmed the extravasation of RBC exposed to oxidative stress across brain endothelium. These findings, demonstrating erythrophagocytosis mediated by the brain endothelial monolayer and the subsequent passage of iron-rich hemoglobin in vitro and RBC in vivo, may have implications for elucidating mechanisms involved in the development of cerebral microbleeds that are not dependent on disruption of the microvasculature.https://www.frontiersin.org/article/10.3389/fncel.2018.00279/fullerythrophagocytosiscerebral microbleedsbrain endothelial cellshemoglobinred blood cellstransmigration |
| spellingShingle | Rudy Chang Juan Castillo Alexander C. Zambon Tatiana B. Krasieva Mark J. Fisher Rachita K. Sumbria Rachita K. Sumbria Brain Endothelial Erythrophagocytosis and Hemoglobin Transmigration Across Brain Endothelium: Implications for Pathogenesis of Cerebral Microbleeds Frontiers in Cellular Neuroscience erythrophagocytosis cerebral microbleeds brain endothelial cells hemoglobin red blood cells transmigration |
| title | Brain Endothelial Erythrophagocytosis and Hemoglobin Transmigration Across Brain Endothelium: Implications for Pathogenesis of Cerebral Microbleeds |
| title_full | Brain Endothelial Erythrophagocytosis and Hemoglobin Transmigration Across Brain Endothelium: Implications for Pathogenesis of Cerebral Microbleeds |
| title_fullStr | Brain Endothelial Erythrophagocytosis and Hemoglobin Transmigration Across Brain Endothelium: Implications for Pathogenesis of Cerebral Microbleeds |
| title_full_unstemmed | Brain Endothelial Erythrophagocytosis and Hemoglobin Transmigration Across Brain Endothelium: Implications for Pathogenesis of Cerebral Microbleeds |
| title_short | Brain Endothelial Erythrophagocytosis and Hemoglobin Transmigration Across Brain Endothelium: Implications for Pathogenesis of Cerebral Microbleeds |
| title_sort | brain endothelial erythrophagocytosis and hemoglobin transmigration across brain endothelium implications for pathogenesis of cerebral microbleeds |
| topic | erythrophagocytosis cerebral microbleeds brain endothelial cells hemoglobin red blood cells transmigration |
| url | https://www.frontiersin.org/article/10.3389/fncel.2018.00279/full |
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