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

Publication date: 31 January 2017
Source:Cell Reports, Volume 18, Issue 5
Author(s): 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 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.

Graphical abstract

Teaser

Endothelial basement membranes are known to restrict leukocyte extravasation; however, how this occurs is unclear. Song et al. show that molecular information gained from basement membrane laminins both directly affects immune cell migration patterns and influences the endothelial barrier properties, thus defining sites where extravasation can occur.


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