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Stabilizing the VE‐cadherin–catenin complex blocks leukocyte extravasation and vascular permeability
Author(s) -
Schulte Dörte,
Küppers Verena,
Dartsch Nina,
Broermann Andre,
Li Hang,
Zarbock Alexander,
Kamenyeva Olena,
Kiefer Friedemann,
Khandoga Alexander,
Massberg Steffen,
Vestweber Dietmar
Publication year - 2011
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2011.304
Subject(s) - biology , extravasation , vascular permeability , leukocyte extravasation , beta catenin , microbiology and biotechnology , cadherin , permeability (electromagnetism) , catenin , immunology , cell adhesion molecule , genetics , signal transduction , cell , wnt signaling pathway , endocrinology , membrane
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.