Stabilizing the VE-cadherin-catenin complex blocks leukocyte extravasation and vascular permeability.

Schulte D, Küppers V, Dartsch N, Broermann A, Li H, Zarbock A, Kamenyeva O, Kiefer F, Khandoga A, Massberg S, Vestweber D

Forschungsartikel (Zeitschrift) | Peer reviewed

Zusammenfassung

To determine whether leukocytes need to open endothelial cell contacts during extravasation, we decided to generate mice with strongly stabilized endothelial junctions. To this end, we replaced VE-cadherin genetically by a VE-cadherin-?-catenin fusion construct. Such mice were completely resistant to the induction of vascular leaks by VEGF or histamine. Neutrophil or lymphocyte recruitment into inflamed cremaster, lung and skin were strongly inhibited in these mice, documenting the importance of the junctional route in vivo. Surprisingly, lymphocyte homing into lymph nodes was not inhibited. VE-cadherin-?-catenin associated more intensely with the actin cytoskeleton as demonstrated by its membrane mobility and detergent extractability. Our results establish the junctional route as the main pathway for extravasating leukocytes in several, although not in all tissues. Furthermore, in these tissues, plasticity of the VE-cadherin-catenin complex is central for the leukocyte diapedesis mechanism.

Details zur Publikation

FachzeitschriftThe EMBO Journal
Jahrgang / Bandnr. / Volume30
Ausgabe / Heftnr. / Issue20
Seitenbereich4157-4170
StatusVeröffentlicht
Veröffentlichungsjahr2011
Sprache, in der die Publikation verfasst istEnglisch
DOI10.1038/emboj.2011.304
StichwörterInflammation; Cells Cultured; Mice; alpha Catenin; Actin Cytoskeleton; Muscle Skeletal; Male; Leukocytes; Capillary Permeability; Animals; Female; Intercellular Junctions; Transendothelial and Transepithelial Migration; Lung; Lymph Nodes; Endothelium Vascular; Antigens CD. Skin; Gene Knock-In Techniques; Cadherins; Inflammation; Cells Cultured; Mice; alpha Catenin; Actin Cytoskeleton; Muscle Skeletal; Male; Leukocytes; Capillary Permeability; Animals; Female; Intercellular Junctions; Transendothelial and Transepithelial Migration; Lung; Lymph Nodes; Endothelium Vascular; Antigens CD. Skin; Gene Knock-In Techniques; Cadherins

Autor*innen der Universität Münster

Kiefer, Friedemann
European Institute of Molecular Imaging (EIMI)
Vestweber, Dietmar
Max-Planck-Institut für Molekulare Biomedizin
Zarbock, Alexander
Klinik für Anästhesiologie, operative Intensivmedizin und Schmerztherapie