title: Stabilizing the VE-cadherin-catenin complex blocks leukocyte extravasation and vascular permeability.
abstract: 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-α-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-α-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.
authors.affiliation: Department of Vascular Cell Biology, Max-Planck-Institute of Molecular Biomedicine, Münster, Germany.
authors.forename: Dörte
authors.initials: D
authors.lastname: Schulte
authors.forename: Verena
authors.initials: V
authors.lastname: Küppers
authors.forename: Nina
authors.initials: N
authors.lastname: Dartsch
authors.forename: Andre
authors.initials: A
authors.lastname: Broermann
authors.forename: Hang
authors.initials: H
authors.lastname: Li
authors.forename: Alexander
authors.initials: A
authors.lastname: Zarbock
authors.forename: Olena
authors.initials: O
authors.lastname: Kamenyeva
authors.forename: Friedemann
authors.initials: F
authors.lastname: Kiefer
authors.forename: Alexander
authors.initials: A
authors.lastname: Khandoga
authors.forename: Steffen
authors.initials: S
authors.lastname: Massberg
authors.forename: Dietmar
authors.initials: D
authors.lastname: Vestweber
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002199:Capillary Permeability; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D055879:Gene Knock-In Techniques; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D007365:Intercellular Junctions / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism / Q000502:physiology*; D008168:Lung / Q000378:metabolism; D008198:Lymph Nodes / Q000378:metabolism; D008297:Male; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism; D012867:Skin / Q000378:metabolism; D057705:Transendothelial and Transepithelial Migration; D051178:alpha Catenin / Q000235:genetics / Q000378:metabolism*; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D051178:alpha Catenin; D000099152:Cadherin 5