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ATP increases the migration of microglia across the brain endothelial cell monolayer

The cerebral microcapillary endothelium, known as the blood–brain barrier (BBB), acts as a barrier between the blood and the interstitial fluid of the brain. The BBB therefore controls the passage of nutrients into the central nervous system (CNS). Microglia show a specific affinity for migration in...

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Autores principales: Maeda, Tomoji, Inagaki, Manato, Fujita, Yu, Kimoto, Takehiro, Tanabe-Fujimura, Chiaki, Zou, Kun, Liu, Junjun, Liu, Shuyu, Komano, Hiroto
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5293564/
https://www.ncbi.nlm.nih.gov/pubmed/26934979
http://dx.doi.org/10.1042/BSR20160054
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author Maeda, Tomoji
Inagaki, Manato
Fujita, Yu
Kimoto, Takehiro
Tanabe-Fujimura, Chiaki
Zou, Kun
Liu, Junjun
Liu, Shuyu
Komano, Hiroto
author_facet Maeda, Tomoji
Inagaki, Manato
Fujita, Yu
Kimoto, Takehiro
Tanabe-Fujimura, Chiaki
Zou, Kun
Liu, Junjun
Liu, Shuyu
Komano, Hiroto
author_sort Maeda, Tomoji
collection PubMed
description The cerebral microcapillary endothelium, known as the blood–brain barrier (BBB), acts as a barrier between the blood and the interstitial fluid of the brain. The BBB therefore controls the passage of nutrients into the central nervous system (CNS). Microglia show a specific affinity for migration into the CNS, and this migration appears to occur independently of BBB integrity. To study the migration of microglia across the BBB, we developed an in vitro co-culture system of mouse brain endothelial cells (MBECs) and Ra2 microglia using Transwell inserts. We first investigated the influence of microglia or ATP, a microglial chemotactic factor, on MBEC barrier integrity. The addition of microglia or ATP led to the disruption of the MBEC monolayer and significantly decreased barrier function as measured by trans-endothelial electrical resistance (TEER) and electric cell–substrate impedance sensing (ECIS). Furthermore, ATP promoted the migration of microglia but not macrophages across the MBEC monolayer. An inhibitor of matrix metalloproteinases (MMPs) decreased the transmigration of microglia in our system, indicating that MMPs play a role in microglial chemotaxis. We specifically identify a role for microglia-derived MMP-2. In conclusion, we offer evidence that microglia migration across the brain endothelial cell monolayer is increased in the presence of ATP in a manner that involves MMP secretion.
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spelling pubmed-52935642017-02-14 ATP increases the migration of microglia across the brain endothelial cell monolayer Maeda, Tomoji Inagaki, Manato Fujita, Yu Kimoto, Takehiro Tanabe-Fujimura, Chiaki Zou, Kun Liu, Junjun Liu, Shuyu Komano, Hiroto Biosci Rep Original Papers The cerebral microcapillary endothelium, known as the blood–brain barrier (BBB), acts as a barrier between the blood and the interstitial fluid of the brain. The BBB therefore controls the passage of nutrients into the central nervous system (CNS). Microglia show a specific affinity for migration into the CNS, and this migration appears to occur independently of BBB integrity. To study the migration of microglia across the BBB, we developed an in vitro co-culture system of mouse brain endothelial cells (MBECs) and Ra2 microglia using Transwell inserts. We first investigated the influence of microglia or ATP, a microglial chemotactic factor, on MBEC barrier integrity. The addition of microglia or ATP led to the disruption of the MBEC monolayer and significantly decreased barrier function as measured by trans-endothelial electrical resistance (TEER) and electric cell–substrate impedance sensing (ECIS). Furthermore, ATP promoted the migration of microglia but not macrophages across the MBEC monolayer. An inhibitor of matrix metalloproteinases (MMPs) decreased the transmigration of microglia in our system, indicating that MMPs play a role in microglial chemotaxis. We specifically identify a role for microglia-derived MMP-2. In conclusion, we offer evidence that microglia migration across the brain endothelial cell monolayer is increased in the presence of ATP in a manner that involves MMP secretion. Portland Press Ltd. 2016-04-15 /pmc/articles/PMC5293564/ /pubmed/26934979 http://dx.doi.org/10.1042/BSR20160054 Text en © 2016 The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution Licence 4.0 (CC BY) (http://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Papers
Maeda, Tomoji
Inagaki, Manato
Fujita, Yu
Kimoto, Takehiro
Tanabe-Fujimura, Chiaki
Zou, Kun
Liu, Junjun
Liu, Shuyu
Komano, Hiroto
ATP increases the migration of microglia across the brain endothelial cell monolayer
title ATP increases the migration of microglia across the brain endothelial cell monolayer
title_full ATP increases the migration of microglia across the brain endothelial cell monolayer
title_fullStr ATP increases the migration of microglia across the brain endothelial cell monolayer
title_full_unstemmed ATP increases the migration of microglia across the brain endothelial cell monolayer
title_short ATP increases the migration of microglia across the brain endothelial cell monolayer
title_sort atp increases the migration of microglia across the brain endothelial cell monolayer
topic Original Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5293564/
https://www.ncbi.nlm.nih.gov/pubmed/26934979
http://dx.doi.org/10.1042/BSR20160054
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