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

Jian Song | Zendy; Xueli Zhang | Zendy; Konrad Buscher | Zendy; Ying Wang | Zendy; Huiyu Wang | Zendy; Jacopo Di Russo | Zendy; Lixia Li | Zendy; Stefan Lütke-Enking | Zendy; Alexander Zarbock | Zendy; Anika Stadtmann | Zendy; Paul Striewski | Zendy; Benedikt Wirth | Zendy; Ivan Kuzmanov | Zendy; Heinz Wiendl | Zendy; Dörte Schulte | Zendy; Dietmar Vestweber | Zendy; Lydia Sorokin | Zendy

Open Access

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

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

Publication year - 2017

Publication title -

cell reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 6.264

H-Index - 154

eISSN - 2639-1856

pISSN - 2211-1247

DOI - 10.1016/j.celrep.2016.12.092

Subject(s) - laminin , extravasation , microbiology and biotechnology , basement membrane , leukocyte extravasation , rhoa , integrin , endothelial stem cell , inflammation , endothelium , cell adhesion , downregulation and upregulation , chemistry , biology , cell adhesion molecule , immunology , cell , signal transduction , in vitro , extracellular matrix , biochemistry , endocrinology , gene

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.

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