Impaired signaling via the high-affinity IgE receptor in Wiskott-Aldrich syndrome protein-deficient mast cells

Vadim I. Pivniouk, Scott B. Snapper, Alexander Kettner, Harri Alenius, Dhafer Laouini, Hervé Falet, John Hartwig, Frederick W. Alt, Raif S. Geha

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

Wiskott-Aldrich syndrome protein (WASP) is the product of the gene deficient in boys with X-linked Wiskott-Aldrich syndrome. We assessed the role of WASP in signaling through the high-affinity IgE receptor (FceRI) using WASP-deficient mice. IgE-dependent degranulation and cytokine secretion were markedly diminished in bone marrow-derived mast cells from WASP-deficient mice. Upstream signaling events that include FceRI-triggered total protein tyrosine phosphorylation, and protein tyrosine phosphorylation of FceRIβ and Syk were not affected by WASP deficiency. However, tyrosine phosphorylation of phospholipase Cγ and Ca2+ mobilization were diminished. IgE-dependent activation of c-Jun N-terminal kinase, cell spreading and redistribution of cellular F-actin in mast cells were reduced in the absence of WASP. We conclude that WASP regulates FceRI-mediated granule exocytosis, cytokine production and cytoskeletal changes in mast cells.

Original languageEnglish (US)
Pages (from-to)1431-1440
Number of pages10
JournalInternational Immunology
Volume15
Issue number12
DOIs
StatePublished - Dec 1 2003

Keywords

  • Allergy and immunology
  • Cell degranulation
  • Receptor-mediated signal transduction
  • Wiskott-Aldrich syndrome

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Pivniouk, V. I., Snapper, S. B., Kettner, A., Alenius, H., Laouini, D., Falet, H., Hartwig, J., Alt, F. W., & Geha, R. S. (2003). Impaired signaling via the high-affinity IgE receptor in Wiskott-Aldrich syndrome protein-deficient mast cells. International Immunology, 15(12), 1431-1440. https://doi.org/10.1093/intimm/dxg148