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

• DOI: 10.1016/j.celrep.2016.12.092
• Publication Date: 2017-01-31T17:31:28Z
• 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
• Keywords: Male; Mice, Knockout; 0301 basic medicine; 0303 health sciences; QH301-705.5; Neutrophils; Endothelial Cells; neutrophil extravasation; Cadherins; Basement Membrane; Mice; 03 medical and health sciences; VE-cadherin; laminin; endothelial basement membrane; Antigens, CD; Cell Movement; Cell Adhesion; Leukocytes; Animals; Endothelium, Vascular; Laminin; Biology (General); Cells, Cultured

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.