Home LiteratureArticle Details

PMID: 14645152 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

International immunology ·Vol. 15 ·No. 12 ·2003-12-00 ·Pages 1431-40

Pivniouk VI, Snapper SB, Kettner A, Alenius H, Laouini D, Falet H, Hartwig J, Alt FW, Geha RS

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 (FcepsilonRI) 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 FcepsilonRI-triggered total protein tyrosine phosphorylation, and protein tyrosine phosphorylation of FcepsilonRIbeta and Syk were not affected by WASP deficiency. However, tyrosine phosphorylation of phospholipase Cgamma and Ca(2+) 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 FcepsilonRI-mediated granule exocytosis, cytokine production and cytoskeletal changes in mast cells.

MeSH Terms

Actins/analysis,metabolism Animals Blotting, Western Bone Marrow Cells/drug effects,metabolism Calcium/metabolism Cell Degranulation/physiology Cell Differentiation/drug effects,genetics Cell Surface Extensions/drug effects Dinitrophenols/immunology,pharmacology Female Flow Cytometry Histamine/blood Immunization, Passive Immunoglobulin E/analysis,immunology,pharmacology Interleukin-3/pharmacology Interleukin-6/genetics,metabolism JNK Mitogen-Activated Protein Kinases Male Mast Cells/chemistry,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,genetics,physiology Proto-Oncogene Proteins/metabolism Proto-Oncogene Proteins c-akt Receptor Aggregation/immunology Receptors, IgE/metabolism,physiology Serum Albumin/pharmacology Signal Transduction/physiology Tumor Necrosis Factor-alpha/metabolism Type C Phospholipases/metabolism Wiskott-Aldrich Syndrome Protein Wiskott-Aldrich Syndrome Protein, Neuronal beta-N-Acetylhexosaminidases/metabolism

Chemicals

Actins Dinitrophenols Interleukin-3 Interleukin-6 Nerve Tissue Proteins Proteins Proto-Oncogene Proteins Receptors, IgE Serum Albumin Tumor Necrosis Factor-alpha Was protein, mouse Wasl protein, mouse Wiskott-Aldrich Syndrome Protein Wiskott-Aldrich Syndrome Protein, Neuronal dinitrophenyl-human serum albumin conjugate Immunoglobulin E Histamine Protein-Tyrosine Kinases Protein Serine-Threonine Kinases Proto-Oncogene Proteins c-akt JNK Mitogen-Activated Protein Kinases Mitogen-Activated Protein Kinases Type C Phospholipases Phospholipase C gamma beta-N-Acetylhexosaminidases Calcium

Authors & Affiliations

9 authors, click to expand affiliations / ORCID

Pivniouk Vadim I

Division of Immunology, Children's Hospital, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA.

Snapper Scott B

Kettner Alexander

Alenius Harri

Laouini Dhafer

Falet Hervé

Hartwig John

Alt Frederick W

Geha Raif S

Article Info

Journal

International immunology

Abbr.

Int Immunol

ISSN

0953-8178

DOI

10.1093/intimm/dxg148

Published

2003-12-00

Pages

1431-40

Language

English

Region

England

NLM ID

8916182

Subset

Grants

NIAID NIH HHS · AI-35714 · United States

External Links

PubMed source DOI: 10.1093/intimm/dxg148 View journal details

Analysis Services

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

Contact

WeChat Official Account