Endothelial Basement Membrane Laminin 511 Contributes to Endothelial Junctional Tightness and Thereby Inhibits Leukocyte Transmigration

Endothelial basement membranes constitute barriers to extravasating leukocytes during inflammation, a process where laminin isoforms define sites of leukocyte exit; however, how this occurs is poorly understood. In addition to a direct effect on leukocyte transmigration, we show that laminin 511 aff...

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Main Authors: Jian Song, Xueli Zhang, Konrad Buscher, Ying Wang, Huiyu Wang, Jacopo Di Russo, Lixia Li, Stefan Lütke-Enking, Alexander Zarbock, Anika Stadtmann, Paul Striewski, Benedikt Wirth, Ivan Kuzmanov, Heinz Wiendl, Dörte Schulte, Dietmar Vestweber, Lydia Sorokin
Format: Article
Language:English
Published: Elsevier 2017-01-01
Series:Cell Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124717300025
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spelling doaj-9c755cef1b5f4844b28c0f18a6db15a12020-11-25T01:15:34ZengElsevierCell Reports2211-12472017-01-011851256126910.1016/j.celrep.2016.12.092Endothelial Basement Membrane Laminin 511 Contributes to Endothelial Junctional Tightness and Thereby Inhibits Leukocyte TransmigrationJian Song0Xueli Zhang1Konrad Buscher2Ying Wang3Huiyu Wang4Jacopo Di Russo5Lixia Li6Stefan Lütke-Enking7Alexander Zarbock8Anika Stadtmann9Paul Striewski10Benedikt Wirth11Ivan Kuzmanov12Heinz Wiendl13Dörte Schulte14Dietmar Vestweber15Lydia Sorokin16Institute of Physiological Chemistry and Pathobiochemistry, University of Muenster, 48149 Muenster, GermanyInstitute of Physiological Chemistry and Pathobiochemistry, University of Muenster, 48149 Muenster, GermanyInstitute of Physiological Chemistry and Pathobiochemistry, University of Muenster, 48149 Muenster, GermanyInstitute of Physiological Chemistry and Pathobiochemistry, University of Muenster, 48149 Muenster, GermanyInstitute of Physiological Chemistry and Pathobiochemistry, University of Muenster, 48149 Muenster, GermanyInstitute of Physiological Chemistry and Pathobiochemistry, University of Muenster, 48149 Muenster, GermanyInstitute of Physiological Chemistry and Pathobiochemistry, University of Muenster, 48149 Muenster, GermanyInstitute of Physiological Chemistry and Pathobiochemistry, University of Muenster, 48149 Muenster, GermanyCells-in-Motion Cluster of Excellence, University of Muenster, 48149 Muenster, GermanyCells-in-Motion Cluster of Excellence, University of Muenster, 48149 Muenster, GermanyCells-in-Motion Cluster of Excellence, University of Muenster, 48149 Muenster, GermanyCells-in-Motion Cluster of Excellence, University of Muenster, 48149 Muenster, GermanyCells-in-Motion Cluster of Excellence, University of Muenster, 48149 Muenster, GermanyCells-in-Motion Cluster of Excellence, University of Muenster, 48149 Muenster, GermanyMax-Planck Institute of Molecular Biomedicine, 48149 Muenster, GermanyCells-in-Motion Cluster of Excellence, University of Muenster, 48149 Muenster, GermanyInstitute of Physiological Chemistry and Pathobiochemistry, University of Muenster, 48149 Muenster, GermanyEndothelial basement membranes constitute barriers to extravasating leukocytes during inflammation, a process where laminin isoforms define sites of leukocyte exit; however, how this occurs is poorly understood. In addition to a direct effect on leukocyte transmigration, we show that laminin 511 affects endothelial barrier function by stabilizing VE-cadherin at junctions and downregulating expression of CD99L2, correlating with reduced neutrophil extravasation. Binding of endothelial cells to laminin 511, but not laminin 411 or non-endothelial laminin 111, enhanced transendothelial cell electrical resistance (TEER) and inhibited neutrophil transmigration. Data suggest that endothelial adhesion to laminin 511 via β1 and β3 integrins mediates RhoA-induced VE-cadherin localization to cell-cell borders, and while CD99L2 downregulation requires integrin β1, it is RhoA-independent. Our data demonstrate that molecular information provided by basement membrane laminin 511 affects leukocyte extravasation both directly and indirectly by modulating endothelial barrier properties.http://www.sciencedirect.com/science/article/pii/S2211124717300025endothelial basement membranelamininVE-cadherinneutrophil extravasation
collection DOAJ
language English
format Article
sources DOAJ
author Jian Song
Xueli Zhang
Konrad Buscher
Ying Wang
Huiyu Wang
Jacopo Di Russo
Lixia Li
Stefan Lütke-Enking
Alexander Zarbock
Anika Stadtmann
Paul Striewski
Benedikt Wirth
Ivan Kuzmanov
Heinz Wiendl
Dörte Schulte
Dietmar Vestweber
Lydia Sorokin
spellingShingle Jian Song
Xueli Zhang
Konrad Buscher
Ying Wang
Huiyu Wang
Jacopo Di Russo
Lixia Li
Stefan Lütke-Enking
Alexander Zarbock
Anika Stadtmann
Paul Striewski
Benedikt Wirth
Ivan Kuzmanov
Heinz Wiendl
Dörte Schulte
Dietmar Vestweber
Lydia Sorokin
Endothelial Basement Membrane Laminin 511 Contributes to Endothelial Junctional Tightness and Thereby Inhibits Leukocyte Transmigration
Cell Reports
endothelial basement membrane
laminin
VE-cadherin
neutrophil extravasation
author_facet Jian Song
Xueli Zhang
Konrad Buscher
Ying Wang
Huiyu Wang
Jacopo Di Russo
Lixia Li
Stefan Lütke-Enking
Alexander Zarbock
Anika Stadtmann
Paul Striewski
Benedikt Wirth
Ivan Kuzmanov
Heinz Wiendl
Dörte Schulte
Dietmar Vestweber
Lydia Sorokin
author_sort Jian Song
title Endothelial Basement Membrane Laminin 511 Contributes to Endothelial Junctional Tightness and Thereby Inhibits Leukocyte Transmigration
title_short Endothelial Basement Membrane Laminin 511 Contributes to Endothelial Junctional Tightness and Thereby Inhibits Leukocyte Transmigration
title_full Endothelial Basement Membrane Laminin 511 Contributes to Endothelial Junctional Tightness and Thereby Inhibits Leukocyte Transmigration
title_fullStr Endothelial Basement Membrane Laminin 511 Contributes to Endothelial Junctional Tightness and Thereby Inhibits Leukocyte Transmigration
title_full_unstemmed Endothelial Basement Membrane Laminin 511 Contributes to Endothelial Junctional Tightness and Thereby Inhibits Leukocyte Transmigration
title_sort endothelial basement membrane laminin 511 contributes to endothelial junctional tightness and thereby inhibits leukocyte transmigration
publisher Elsevier
series Cell Reports
issn 2211-1247
publishDate 2017-01-01
description Endothelial basement membranes constitute barriers to extravasating leukocytes during inflammation, a process where laminin isoforms define sites of leukocyte exit; however, how this occurs is poorly understood. In addition to a direct effect on leukocyte transmigration, we show that laminin 511 affects endothelial barrier function by stabilizing VE-cadherin at junctions and downregulating expression of CD99L2, correlating with reduced neutrophil extravasation. Binding of endothelial cells to laminin 511, but not laminin 411 or non-endothelial laminin 111, enhanced transendothelial cell electrical resistance (TEER) and inhibited neutrophil transmigration. Data suggest that endothelial adhesion to laminin 511 via β1 and β3 integrins mediates RhoA-induced VE-cadherin localization to cell-cell borders, and while CD99L2 downregulation requires integrin β1, it is RhoA-independent. Our data demonstrate that molecular information provided by basement membrane laminin 511 affects leukocyte extravasation both directly and indirectly by modulating endothelial barrier properties.
topic endothelial basement membrane
laminin
VE-cadherin
neutrophil extravasation
url http://www.sciencedirect.com/science/article/pii/S2211124717300025
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