TPC1 deficiency or blockade augments systemic anaphylaxis and mast cell activity

Medientyp: E-Artikel
Titel: TPC1 deficiency or blockade augments systemic anaphylaxis and mast cell activity
Beteiligte: Arlt, Elisabeth; Fraticelli, Marco; Tsvilovskyy, Volodymyr; Nadolni, Wiebke; Breit, Andreas; O’Neill, Thomas J.; Resenberger, Stefanie; Wennemuth, Gunther; Wahl-Schott, Christian; Biel, Martin; Grimm, Christian; Freichel, Marc; Gudermann, Thomas; Klugbauer, Norbert; Boekhoff, Ingrid; Zierler, Susanna
Erschienen: Proceedings of the National Academy of Sciences, 2020
Erschienen in: Proceedings of the National Academy of Sciences, 117 (2020) 30, Seite 18068-18078
Sprache: Englisch
DOI: 10.1073/pnas.1920122117
ISSN: 1091-6490; 0027-8424
Entstehung:
Anmerkungen:
Beschreibung: Significance The worldwide prevalence of allergic and anaphylactic reactions has increased massively over recent decades. Mast cells and basophils are essential drivers of these diseases, releasing inflammatory mediators such as histamine. Here, we link the endolysosomal two-pore channel TPC1 to systemic anaphylaxis in vivo and underlying mast cell function ex vivo. TPC1-deficient mice develop enhanced systemic anaphylaxis reflected by a drop in body temperature and slower recovery compared to wild-type animals. Genetic deletion or pharmacological inhibition of TPC1 enhances mast cell degranulation and histamine release due to accelerated calcium release, mainly from the endoplasmic reticulum. Accordingly, it is tempting to speculate that activation of TPC1 ameliorates mast cell degranulation, highlighting TPC1 as a potential drug target against allergic hypersensitivity.
Zugangsstatus: Freier Zugang

Nur in Feld suchen:

Zuletzt gesuchte Begriffe: