Title: Increased IgE-dependent mast cell activation and anaphylactic responses in mice lacking the calcium-activated nonselective cation channel TRPM4
Authors: Vennekens, Rudi ×
Olausson, Jenny
Meissner, Marcel
Bloch, Wilhelm
Mathar, Ilka
Philipp, Stephan E
Schmitz, Frank
Weissgerber, Petra
Nilius, Bernd
Flockerzi, Veit
Freichel, Marc #
Issue Date: 1-Feb-2007
Series Title: Nature Immunology vol:8 issue:3 pages:312-320
Abstract: Mast cells are key effector cells in allergic reactions. Aggregation of the receptor FcepsilonRI in mast cells triggers the influx of calcium (Ca(2+)) and the release of inflammatory mediators. Here we show that transient receptor potential TRPM4 proteins acted as calcium-activated nonselective cation channels and critically determined the driving force for Ca(2+) influx in mast cells. Trpm4(-/-) bone marrow-derived mast cells had more Ca(2+) entry than did TRPM4(+/+) cells after FcepsilonRI stimulation. Consequently, Trpm4(-/-) bone marrow-derived mast cells had augmented degranulation and released more histamine, leukotrienes and tumor necrosis factor. Trpm4(-/-) mice had a more severe IgE-mediated acute passive cutaneous anaphylactic response, whereas late-phase passive cutaneous anaphylaxis was not affected. Our results establish the physiological function of TRPM4 channels as critical regulators of Ca(2+) entry in mast cells.
ISSN: 1529-2908
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Physiology Section (-)
Department of Cellular and Molecular Medicine - miscellaneous
Laboratory of Ion Channel Research
× corresponding author
# (joint) last author

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