Article abstract
Nature Immunology 8, 312 - 320 (2007)
Published online: 11 February 2007 | doi:10.1038/ni1441
Increased IgE-dependent mast cell activation and anaphylactic responses in mice lacking the calcium-activated nonselective cation channel TRPM4
Rudi Vennekens1,2, Jenny Olausson2, Marcel Meissner2, Wilhelm Bloch3, Ilka Mathar2, Stephan E Philipp2, Frank Schmitz4, Petra Weissgerber2, Bernd Nilius1, Veit Flockerzi2 & Marc Freichel2
Abstract
Mast cells are key effector cells in allergic reactions. Aggregation of the receptor Fc
RI in mast cells triggers the influx of calcium (Ca2+) 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 Ca2+ influx in mast cells. Trpm4-/- bone marrow–derived mast cells had more Ca2+ entry than did TRPM4+/+ cells after FcRI 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 Ca2+ entry in mast cells.
- Laboratory of Ion Channel Research, Division of Physiology, Department of Molecular Cell Biology, Campus Gasthuisberg, O&N1, KU Leuven, Herestraat 49 bus 802, B-3000 Leuven, Belgium.
- Experimentelle und Klinische Pharmakologie und Toxikologie, Universität des Saarlandes, D-66421 Homburg, Germany.
- Institut für Kreislaufforschung und Sportmedizin, Molekulare und Zelluläre Sportmedizin, Deutsche Sporthochschule, 50927 Köln, Germany.
- Anatomisches Institut, Universität des Saarlandes, D-66421 Homburg, Germany.
Correspondence to: Rudi Vennekens1,2 e-mail: rudi.vennekens@med.kuleuven.be
Correspondence to: Marc Freichel2 e-mail: marc.freichel@uniklinikum-saarland.de
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