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

• Published in: International immunology 2003-12, Vol.15 (12), p.1431-1440
• Main Authors: Pivniouk, Vadim I., Snapper, Scott B., Kettner, Alexander, Alenius, Harri, Laouini, Dhafer, Falet, Hervé, Hartwig, John, Alt, Frederick W., Geha, Raif S.
• Format: Article
• Language: English
• Subjects: Actins - analysis; Actins - metabolism; allergy and immunology; Animals; beta-N-Acetylhexosaminidases - metabolism; Blotting, Western; Bone Marrow Cells - drug effects; Bone Marrow Cells - metabolism; Calcium - metabolism; cell degranulation; Cell Degranulation - physiology; Cell Differentiation - drug effects; Cell Differentiation - genetics; Cell Surface Extensions - drug effects; Dinitrophenols - immunology; Dinitrophenols - pharmacology; Female; Flow Cytometry; Histamine - blood; Immunization, Passive; Immunoglobulin E - analysis; Immunoglobulin E - immunology; Immunoglobulin E - pharmacology; Interleukin-3 - pharmacology; Interleukin-6 - genetics; Interleukin-6 - metabolism; JNK Mitogen-Activated Protein Kinases; Male; Mast Cells - chemistry; Mast Cells - physiology; Mice; Mice, Knockout; Microscopy, Fluorescence; Mitogen-Activated Protein Kinases - metabolism; Nerve Tissue Proteins - analysis; Phospholipase C gamma; Phosphorylation; Protein-Serine-Threonine Kinases - metabolism; Protein-Tyrosine Kinases - metabolism; Proteins - analysis; Proteins - genetics; Proteins - physiology; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-akt; Receptor Aggregation - immunology; Receptors, IgE - metabolism; Receptors, IgE - physiology; receptor‐mediated signal transduction; Serum Albumin - pharmacology; Signal Transduction - physiology; Tumor Necrosis Factor-alpha - metabolism; Type C Phospholipases - metabolism; Wiskott-Aldrich Syndrome Protein; Wiskott-Aldrich Syndrome Protein, Neuronal; Wiskott–Aldrich syndrome
• ISSN: 0953-8178; 1460-2377; 1460-2377
• DOI: 10.1093/intimm/dxg148

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 (FcϵRI) 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 FcϵRI‐triggered total protein tyrosine phosphorylation, and protein tyrosine phosphorylation of FcϵRIβ 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 FcϵRI‐mediated granule exocytosis, cytokine production and cytoskeletal changes in mast cells.