FcεRI-induced activation by low antigen concentrations results in nuclear signals in the absence of degranulation

Ana Grodzki, Kyungduk D. Moon, Elsa H. Berenstein, Reuben P. Siraganian

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

High affinity IgE receptor (FcεRI)-induced activation of mast cells results in degranulation and generation of leukotrienes and cytokines. FcεRI-induced mast cell activation was analyzed at a single cell basis using a rat basophilic leukemia (RBL-2H3) cell line transfected with a reporter plasmid containing three tandem NFAT (nuclear factor of activated T cells) binding sites fused to enhanced green fluorescent protein (GFP). Surprisingly, with this sensitive detection system, there is activation of IgE sensitized cells at concentrations of antigen as low as 10 pg/ml, which was 10-fold lower than was detected by degranulation. There were differences in signaling pathways leading to degranulation compared to NFAT-mediated gene activation. Both signaling to NFAT activation and degranulation required Syk and calcineurin. However inhibitors of the phosphatidylinositol 3-kinase pathway blocked degranulation but did not NFAT activation. The results also indicate that NFAT was activated at lower intracellular signals compared to degranulation. Therefore, FcεRI activation can result in nuclear signals in the absence of the release of mediators.

Original languageEnglish (US)
Pages (from-to)2539-2547
Number of pages9
JournalMolecular Immunology
Volume46
Issue number13
DOIs
StatePublished - Aug 1 2009
Externally publishedYes

Keywords

  • Degranulation
  • FcεRI
  • Mast cells
  • NFAT signaling
  • Signal transduction

ASJC Scopus subject areas

  • Immunology
  • Molecular Biology

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