Increased Transendothelial Transport of CCL3 Is Insufficient to Drive Immune Cell Transmigration through the Blood–Brain Barrier under Inflammatory Conditions In VitroReportar como inadecuado




Increased Transendothelial Transport of CCL3 Is Insufficient to Drive Immune Cell Transmigration through the Blood–Brain Barrier under Inflammatory Conditions In Vitro - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Mediators of Inflammation - Volume 2017 2017, Article ID 6752756, 11 pages - https:-doi.org-10.1155-2017-6752756

Research Article

Laboratory of Experimental Hematology, Vaccine and Infectious Disease Institute VAXINFECTIO, Faculty of Medicine and Health Sciences, University of Antwerp, 2610 Wilrijk, Belgium

Laboratory of Cell Biology and Histology, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, 2610 Wilrijk, Belgium

Center for Cell Therapy and Regenerative Medicine, Antwerp University Hospital, 2650 Edegem, Belgium

Correspondence should be addressed to Nathalie Cools

Received 10 November 2016; Revised 20 March 2017; Accepted 27 March 2017; Published 25 May 2017

Academic Editor: Karsten Ruscher

Copyright © 2017 Maxime De Laere et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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.





Autor: Maxime De Laere, Carmelita Sousa, Megha Meena, Roeland Buckinx, Jean-Pierre Timmermans, Zwi Berneman, and Nathalie Cools

Fuente: https://www.hindawi.com/



DESCARGAR PDF




Documentos relacionados