We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- 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
- 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.
- Publication
Nature immunology, 2007, Vol 8, Issue 3, p312
- ISSN
1529-2908
- Publication type
Journal Article
- DOI
10.1038/ni1441