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lüll Nascent endothelium initiates Th2 polarization of asthma Asosingh K; Cheng G; Xu W; Savasky BM; Aronica MA; Li X; Erzurum SCJ Immunol 2013[Apr]; 190 (7): 3458-65Asthma airway remodeling is linked to Th2 inflammation. Angiogenesis is a consistent feature of airway remodeling, but its contribution to pathophysiology remains unclear. We hypothesized that nascent endothelial cells in newly forming vessels are sufficient to initiate Th2-inflammation. Vascular endothelial (VE)-cadherin is a constitutively expressed endothelial cell adhesion molecule that is exposed in its monomer form on endothelial tip cells prior to adherens junction formation. Abs targeted to VE-cadherin monomers inhibit angiogenesis by blocking this adherens junction formation. In this study, VE-cadherin monomer Ab reduced angiogenesis in the lungs of the allergen-induced murine asthma model. Strikingly, Th2 responses including, IgE production, eosinophil infiltration of the airway, subepithelial fibrosis, mucus metaplasia, and airway-hyperreactivity were also attenuated by VE-cadherin blockade, via mechanisms that blunted endothelial IL-25 and proangiogenic progenitor cell thymic stromal lymphopoietin production. The results identify angiogenic responses in the origins of atopic inflammation.|Airway Remodeling/drug effects/immunology[MESH]|Allergens/immunology[MESH]|Animals[MESH]|Antibodies, Monoclonal/pharmacology[MESH]|Antigens, CD[MESH]|Asthma/*immunology/metabolism[MESH]|Bone Marrow Cells/immunology[MESH]|Cadherins/antagonists & inhibitors[MESH]|Cytokines/immunology/metabolism[MESH]|Disease Models, Animal[MESH]|Endothelial Cells/immunology/metabolism[MESH]|Endothelium/*immunology/metabolism[MESH]|Female[MESH]|Hematopoietic Stem Cells/immunology/metabolism[MESH]|Immunoglobulin E/immunology[MESH]|Interleukins/metabolism[MESH]|Lung/immunology/metabolism[MESH]|Mice[MESH]|Neovascularization, Physiologic/drug effects[MESH]|Phenotype[MESH]|STAT6 Transcription Factor/metabolism[MESH]|Th2 Cells/*immunology/metabolism[MESH]|Thymic Stromal Lymphopoietin[MESH] |