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

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

doi:10.1016/j.celrep.2016.12.092

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

Cell Rep. 2017 Jan 31;18(5):1256-1269. doi: 10.1016/j.celrep.2016.12.092.

Authors

Jian Song¹, Xueli Zhang¹, Konrad Buscher¹, Ying Wang¹, Huiyu Wang¹, Jacopo Di Russo¹, Lixia Li¹, Stefan Lütke-Enking¹, Alexander Zarbock², Anika Stadtmann², Paul Striewski³, Benedikt Wirth³, Ivan Kuzmanov⁴, Heinz Wiendl⁴, Dörte Schulte⁵, Dietmar Vestweber⁶, Lydia Sorokin⁷

Affiliations

¹ Institute of Physiological Chemistry and Pathobiochemistry, University of Muenster, 48149 Muenster, Germany; Cells-in-Motion Cluster of Excellence, University of Muenster, 48149 Muenster, Germany.
² Cells-in-Motion Cluster of Excellence, University of Muenster, 48149 Muenster, Germany; Department of Anesthesiology and Intensive Care Medicine, University of Muenster, 48149 Muenster, Germany.
³ Cells-in-Motion Cluster of Excellence, University of Muenster, 48149 Muenster, Germany; Institute for Computational and Applied Mathematics, University of Muenster, 48149 Muenster, Germany.
⁴ Cells-in-Motion Cluster of Excellence, University of Muenster, 48149 Muenster, Germany; Department of Neurology, University Hospital of Muenster, University of Muenster, 48149 Muenster, Germany.
⁵ Max-Planck Institute of Molecular Biomedicine, 48149 Muenster, Germany.
⁶ Cells-in-Motion Cluster of Excellence, University of Muenster, 48149 Muenster, Germany; Max-Planck Institute of Molecular Biomedicine, 48149 Muenster, Germany.
⁷ Institute of Physiological Chemistry and Pathobiochemistry, University of Muenster, 48149 Muenster, Germany; Cells-in-Motion Cluster of Excellence, University of Muenster, 48149 Muenster, Germany. Electronic address: sorokin@uni-muenster.de.

PMID: 28147279
DOI: 10.1016/j.celrep.2016.12.092

Abstract

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.

Keywords: VE-cadherin; endothelial basement membrane; laminin; neutrophil extravasation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antigens, CD / metabolism
Basement Membrane / metabolism*
Cadherins / metabolism
Cell Adhesion / physiology
Cell Movement / physiology*
Cells, Cultured
Endothelial Cells / metabolism*
Endothelium, Vascular / metabolism*
Laminin / metabolism*
Leukocytes / metabolism*
Male
Mice
Mice, Knockout
Neutrophils / metabolism
Neutrophils / physiology

Substances

Antigens, CD
Cadherins
Laminin
cadherin 5
laminin 10