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Transient targeting of phosphoinositide 3-kinase acts as a roadblock in mast cells’ route to allergy

Collman, Emilie and Bohnacker, Thomas and Marone, Romina and Dawson King, Janet and Rehburg, Markus and Stringer, Rowan and Krombach, Fritz and Burkhart, Christoph and Hirsch, Emilio and Hollingworth, Greg and Thomas, Matthew and Wymann, Matthias (2013) Transient targeting of phosphoinositide 3-kinase acts as a roadblock in mast cells’ route to allergy. Journal of Allergy and Clinical Immunology, 132 (4). pp. 959-968. ISSN 00916749

Abstract

Functional PI3Kγ, but not PI3Kδ, was crucial for mast cell accumulation in IgE-challenged skin, TNF-α release from IgE/antigen-stimulated mast cells, and mast cell/endothelial interactions and chemotaxis. PI3Kγ-deficient bone marrow–derived mast cells did not adhere to the endothelium in TNF-α–treated cremaster muscle, whereas PI3Kδ was not required. Depletion of TNF-α blocked IgE-induced mast cell recruitment, which links tissue mast cell–derived cytokine release to endothelial activation and mast cell recruitment. Interference with mast cell recruitment protected against anaphylaxis and was superior to blockage of tissue mast cell degranulation.

Item Type: Article
Additional Information: NVS-PI3-4 is a synonym which will replace the blinding code HBC520 in the figs file in the final document
Keywords: Mast cells, allergy, PI3 Kinase gamma
Date Deposited: 01 Jul 2017 00:45
Last Modified: 01 Jul 2017 00:45
URI: https://oak.novartis.com/id/eprint/7941

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