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Luminal decoration of blood vessels by activated perivasal mast cells in allergic rhinitis

Schaefer, Thorsten and Lorentz, Pascal and Zajonz, Alexandra and Bohnacker, Thomas and Wymann, Matthias and Schweighoffer, Tamas (2012) Luminal decoration of blood vessels by activated perivasal mast cells in allergic rhinitis. Allergy. ISSN 0105-4538

Abstract

In allergic diseases, like in rhinitis, antigen challenge induces rapid degranulation of tissue resident mast cells and subsequent recruitment of leukocytes in response to soluble immunmodulators. The fate of mast cell-derived, membrane associated factors in inflamed tissue remained however unresolved. By tracking CD63var, a unique marker of mast cell granular membrane, we discovered that selected mast cell membrane components appeared on the surface of distinct bystander cells. Acceptor cells did not acquire these molecules simply by uptake of soluble material or in the form of exosomes. Instead, physically stable cell-to-cell contact was required for transfer, in which a Notch2-Jagged1 interaction played a decisive role. This process is activation-dependent, unidirectional, and involves a unique membrane topology. Endothelial cells were particularly efficient acceptors. In organotypic 3D in vitro cultures we found that transferred mast cell molecules traversed an endothelial monolayer, and reappeared focally compacted on its distal surface, away from the actual contact zone. Moreover, we observed that such mast cell-derived membrane patches decorate microcapillaries in the nasal mucosa of allergic rhinitis patients. Direct membrane transfer from perivasal mast cells into nearby blood vessels thus constitutes a novel mechanism to modulate endothelial surface features with apparent significance in allergic diseases.

Item Type: Article
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Additional Information: archiving not allowed on institutional repository
Keywords: Mast Cell, Endothelial Cell, Inflammation
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Date Deposited: 13 Oct 2015 13:15
Last Modified: 13 Oct 2015 13:15
URI: https://oak.novartis.com/id/eprint/4200

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