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 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.
Institute of Physiological Chemistry and Pathobiochemistry, University of Muenster, 48149 Muenster, Germany; Cells-in-Motion Cluster of Excellence, University of Muenster, 48149 Muenster, Germany.
Jian
J
Song
Institute of Physiological Chemistry and Pathobiochemistry, University of Muenster, 48149 Muenster, Germany; Cells-in-Motion Cluster of Excellence, University of Muenster, 48149 Muenster, Germany.
Xueli
X
Zhang
Institute of Physiological Chemistry and Pathobiochemistry, University of Muenster, 48149 Muenster, Germany; Cells-in-Motion Cluster of Excellence, University of Muenster, 48149 Muenster, Germany.
Konrad
K
Buscher
Institute of Physiological Chemistry and Pathobiochemistry, University of Muenster, 48149 Muenster, Germany; Cells-in-Motion Cluster of Excellence, University of Muenster, 48149 Muenster, Germany.
Ying
Y
Wang
Institute of Physiological Chemistry and Pathobiochemistry, University of Muenster, 48149 Muenster, Germany; Cells-in-Motion Cluster of Excellence, University of Muenster, 48149 Muenster, Germany.
Huiyu
H
Wang
Institute of Physiological Chemistry and Pathobiochemistry, University of Muenster, 48149 Muenster, Germany; Cells-in-Motion Cluster of Excellence, University of Muenster, 48149 Muenster, Germany.
Jacopo
J
Di Russo
Institute of Physiological Chemistry and Pathobiochemistry, University of Muenster, 48149 Muenster, Germany; Cells-in-Motion Cluster of Excellence, University of Muenster, 48149 Muenster, Germany.
Lixia
L
Li
Institute of Physiological Chemistry and Pathobiochemistry, University of Muenster, 48149 Muenster, Germany; Cells-in-Motion Cluster of Excellence, University of Muenster, 48149 Muenster, Germany.
Stefan
S
Lütke-Enking
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.
Alexander
A
Zarbock
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.
Anika
A
Stadtmann
Cells-in-Motion Cluster of Excellence, University of Muenster, 48149 Muenster, Germany; Institute for Computational and Applied Mathematics, University of Muenster, 48149 Muenster, Germany.
Paul
P
Striewski
Cells-in-Motion Cluster of Excellence, University of Muenster, 48149 Muenster, Germany; Institute for Computational and Applied Mathematics, University of Muenster, 48149 Muenster, Germany.
Benedikt
B
Wirth
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.
Ivan
I
Kuzmanov
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.
Heinz
H
Wiendl
Max-Planck Institute of Molecular Biomedicine, 48149 Muenster, Germany.
Dörte
D
Schulte
Cells-in-Motion Cluster of Excellence, University of Muenster, 48149 Muenster, Germany; Max-Planck Institute of Molecular Biomedicine, 48149 Muenster, Germany.
Dietmar
D
Vestweber
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.
Lydia
L
Sorokin
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001485:Basement Membrane / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism*; D007797:Laminin / Q000378:metabolism*; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000378:metabolism / Q000502:physiology; D000099152:Cadherin 5
D015703:Antigens, CD; D015820:Cadherins; D007797:Laminin; D000099152:Cadherin 5; C119013:laminin 10
VE-cadherin; endothelial basement membrane; laminin; neutrophil extravasation