Increased Transendothelial Transport of CCL3 Is Insufficient to Drive Immune Cell Transmigration through the Blood–Brain Barrier under Inflammatory Conditions In Vitro
Many neuroinflammatory diseases are characterized by massive immune cell infiltration into the central nervous system. Identifying the underlying mechanisms could aid in the development of therapeutic strategies specifically interfering with inflammatory cell trafficking. To achieve this, we impleme...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2017-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2017/6752756 |
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| author | Maxime De Laere Carmelita Sousa Megha Meena Roeland Buckinx Jean-Pierre Timmermans Zwi Berneman Nathalie Cools |
| author_facet | Maxime De Laere Carmelita Sousa Megha Meena Roeland Buckinx Jean-Pierre Timmermans Zwi Berneman Nathalie Cools |
| author_sort | Maxime De Laere |
| collection | DOAJ |
| description | Many neuroinflammatory diseases are characterized by massive immune cell infiltration into the central nervous system. Identifying the underlying mechanisms could aid in the development of therapeutic strategies specifically interfering with inflammatory cell trafficking. To achieve this, we implemented and validated a blood–brain barrier (BBB) model to study chemokine secretion, chemokine transport, and leukocyte trafficking in vitro. In a coculture model consisting of a human cerebral microvascular endothelial cell line and human astrocytes, proinflammatory stimulation downregulated the expression of tight junction proteins, while the expression of adhesion molecules and chemokines was upregulated. Moreover, chemokine transport across BBB cocultures was upregulated, as evidenced by a significantly increased concentration of the inflammatory chemokine CCL3 at the luminal side following proinflammatory stimulation. CCL3 transport occurred independently of the chemokine receptors CCR1 and CCR5, albeit that migrated cells displayed increased expression of CCR1 and CCR5. However, overall leukocyte transmigration was reduced in inflammatory conditions, although higher numbers of leukocytes adhered to activated endothelial cells. Altogether, our findings demonstrate that prominent barrier activation following proinflammatory stimulation is insufficient to drive immune cell recruitment, suggesting that additional traffic cues are crucial to mediate the increased immune cell infiltration seen in vivo during neuroinflammation. |
| format | Article |
| id | doaj-art-ce41a404e0ee400a8db9b19e2711c9c3 |
| institution | DOAJ |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-ce41a404e0ee400a8db9b19e2711c9c32025-08-20T03:19:42ZengWileyMediators of Inflammation0962-93511466-18612017-01-01201710.1155/2017/67527566752756Increased Transendothelial Transport of CCL3 Is Insufficient to Drive Immune Cell Transmigration through the Blood–Brain Barrier under Inflammatory Conditions In VitroMaxime De Laere0Carmelita Sousa1Megha Meena2Roeland Buckinx3Jean-Pierre Timmermans4Zwi Berneman5Nathalie Cools6Laboratory of Experimental Hematology, Vaccine & Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, University of Antwerp, 2610 Wilrijk, BelgiumLaboratory of Experimental Hematology, Vaccine & Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, University of Antwerp, 2610 Wilrijk, BelgiumLaboratory of Experimental Hematology, Vaccine & Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, University of Antwerp, 2610 Wilrijk, BelgiumLaboratory of Cell Biology and Histology, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, 2610 Wilrijk, BelgiumLaboratory of Cell Biology and Histology, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, 2610 Wilrijk, BelgiumLaboratory of Experimental Hematology, Vaccine & Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, University of Antwerp, 2610 Wilrijk, BelgiumLaboratory of Experimental Hematology, Vaccine & Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, University of Antwerp, 2610 Wilrijk, BelgiumMany neuroinflammatory diseases are characterized by massive immune cell infiltration into the central nervous system. Identifying the underlying mechanisms could aid in the development of therapeutic strategies specifically interfering with inflammatory cell trafficking. To achieve this, we implemented and validated a blood–brain barrier (BBB) model to study chemokine secretion, chemokine transport, and leukocyte trafficking in vitro. In a coculture model consisting of a human cerebral microvascular endothelial cell line and human astrocytes, proinflammatory stimulation downregulated the expression of tight junction proteins, while the expression of adhesion molecules and chemokines was upregulated. Moreover, chemokine transport across BBB cocultures was upregulated, as evidenced by a significantly increased concentration of the inflammatory chemokine CCL3 at the luminal side following proinflammatory stimulation. CCL3 transport occurred independently of the chemokine receptors CCR1 and CCR5, albeit that migrated cells displayed increased expression of CCR1 and CCR5. However, overall leukocyte transmigration was reduced in inflammatory conditions, although higher numbers of leukocytes adhered to activated endothelial cells. Altogether, our findings demonstrate that prominent barrier activation following proinflammatory stimulation is insufficient to drive immune cell recruitment, suggesting that additional traffic cues are crucial to mediate the increased immune cell infiltration seen in vivo during neuroinflammation.http://dx.doi.org/10.1155/2017/6752756 |
| spellingShingle | Maxime De Laere Carmelita Sousa Megha Meena Roeland Buckinx Jean-Pierre Timmermans Zwi Berneman Nathalie Cools Increased Transendothelial Transport of CCL3 Is Insufficient to Drive Immune Cell Transmigration through the Blood–Brain Barrier under Inflammatory Conditions In Vitro Mediators of Inflammation |
| title | Increased Transendothelial Transport of CCL3 Is Insufficient to Drive Immune Cell Transmigration through the Blood–Brain Barrier under Inflammatory Conditions In Vitro |
| title_full | Increased Transendothelial Transport of CCL3 Is Insufficient to Drive Immune Cell Transmigration through the Blood–Brain Barrier under Inflammatory Conditions In Vitro |
| title_fullStr | Increased Transendothelial Transport of CCL3 Is Insufficient to Drive Immune Cell Transmigration through the Blood–Brain Barrier under Inflammatory Conditions In Vitro |
| title_full_unstemmed | Increased Transendothelial Transport of CCL3 Is Insufficient to Drive Immune Cell Transmigration through the Blood–Brain Barrier under Inflammatory Conditions In Vitro |
| title_short | Increased Transendothelial Transport of CCL3 Is Insufficient to Drive Immune Cell Transmigration through the Blood–Brain Barrier under Inflammatory Conditions In Vitro |
| title_sort | increased transendothelial transport of ccl3 is insufficient to drive immune cell transmigration through the blood brain barrier under inflammatory conditions in vitro |
| url | http://dx.doi.org/10.1155/2017/6752756 |
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