Essential function for the calcium sensor STIM1 in mast cell activation and anaphylactic responses
Mast cells have key functions as effectors of immunoglobulin E–mediated allergic
inflammatory diseases. Allergen stimulation induces Ca2+ influx and elicits the secretion of
inflammatory mediators from mast cells. Here we show that the Ca2+-binding endoplasmic
reticulum protein STIM1 is critical to mast cell function. STIM1-deficient fetal liver–derived
mast cells had impaired Ca2+ influx mediated by the high-affinity immunoglobulin E receptor
FcεRI and activation of the transcription factors NF-κB and NFAT. Mast cells lacking STIM1 …
inflammatory diseases. Allergen stimulation induces Ca2+ influx and elicits the secretion of
inflammatory mediators from mast cells. Here we show that the Ca2+-binding endoplasmic
reticulum protein STIM1 is critical to mast cell function. STIM1-deficient fetal liver–derived
mast cells had impaired Ca2+ influx mediated by the high-affinity immunoglobulin E receptor
FcεRI and activation of the transcription factors NF-κB and NFAT. Mast cells lacking STIM1 …
Abstract
Mast cells have key functions as effectors of immunoglobulin E–mediated allergic inflammatory diseases. Allergen stimulation induces Ca2+ influx and elicits the secretion of inflammatory mediators from mast cells. Here we show that the Ca2+-binding endoplasmic reticulum protein STIM1 is critical to mast cell function. STIM1-deficient fetal liver–derived mast cells had impaired Ca2+ influx mediated by the high-affinity immunoglobulin E receptor FcεRI and activation of the transcription factors NF-κB and NFAT. Mast cells lacking STIM1 also had much less degranulation and cytokine production after FcεRI stimulation. In addition, alterations in STIM1 expression affected the sensitivity of immunoglobulin E–mediated immediate-phase anaphylactic responses in vivo. Thus, STIM1 is key in promoting the Ca2+ influx that is essential for FcεRI-mediated mast cell activation and anaphylaxis.
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