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WIP regulates signaling via the high affinity receptor for immunoglobulin E in mast cells.

Kettner A, Kumar L, Antón IM, Sasahara Y, de la Fuente M, Pivniouk VI, Falet H, Hartwig JH, Geha RS - J. Exp. Med. (2004)

Bottom Line: Calcium mobilization, phosphorylation of Syk, phospholipase C-g2, and c-Jun NH2-terminal kinase were markedly decreased in WIP-deficient BMMCs.However, the kinetics of actin changes and the cell shape changes that follow FcepsilonRI signaling were altered in WIP-deficient BMMCs.These results suggest that WIP regulates FcepsilonRI-mediated mast cell activation by regulating Syk levels and actin cytoskeleton rearrangement.

View Article: PubMed Central - PubMed

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

ABSTRACT
Wiskott-Aldrich syndrome protein-interacting protein (WIP) stabilizes actin filaments and is important for immunoreceptor-mediated signal transduction leading to actin cytoskeleton rearrangement in T and B cells. Here we report a role for WIP in signaling pathways downstream of the high affinity receptor for immunoglobulin (Ig)E (FcepsilonRI) in mast cells. WIP-deficient bone marrow-derived mast cells (BMMCs) were impaired in their capacity to degranulate and secrete interleukin 6 after FcepsilonRI ligation. Calcium mobilization, phosphorylation of Syk, phospholipase C-g2, and c-Jun NH2-terminal kinase were markedly decreased in WIP-deficient BMMCs. WIP was found to associate with Syk after FcepsilonRI ligation and to inhibit Syk degradation as evidenced by markedly diminished Syk levels in WIP-deficient BMMCs. WIP-deficient BMMCs exhibited no apparent defect in their subcortical actin network and were normal in their ability to form protrusions when exposed to an IgE-coated surface. However, the kinetics of actin changes and the cell shape changes that follow FcepsilonRI signaling were altered in WIP-deficient BMMCs. These results suggest that WIP regulates FcepsilonRI-mediated mast cell activation by regulating Syk levels and actin cytoskeleton rearrangement.

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IgE-mediated IL-6 release of WIP−/− BMMCs. IL-6 release by BMMCs. BMMCs preloaded with IgE were incubated with F(ab′)2 anti–rat Ig for 24 h. IL-6 release was determined by ELISA. Results represent mean ± SD of three experiments. Statistical analysis was performed using the Student's t test.
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fig3: IgE-mediated IL-6 release of WIP−/− BMMCs. IL-6 release by BMMCs. BMMCs preloaded with IgE were incubated with F(ab′)2 anti–rat Ig for 24 h. IL-6 release was determined by ELISA. Results represent mean ± SD of three experiments. Statistical analysis was performed using the Student's t test.

Mentions: To assess the role of WIP in FcεRI-mediated cytokine production, IL-6 concentration was measured in cell culture supernatants of BMMCs 24 h after stimulation. WIP−/− BMMCs secreted markedly less IL-6 than WT controls at all concentrations of cross-linker used (Fig. 3).


WIP regulates signaling via the high affinity receptor for immunoglobulin E in mast cells.

Kettner A, Kumar L, Antón IM, Sasahara Y, de la Fuente M, Pivniouk VI, Falet H, Hartwig JH, Geha RS - J. Exp. Med. (2004)

IgE-mediated IL-6 release of WIP−/− BMMCs. IL-6 release by BMMCs. BMMCs preloaded with IgE were incubated with F(ab′)2 anti–rat Ig for 24 h. IL-6 release was determined by ELISA. Results represent mean ± SD of three experiments. Statistical analysis was performed using the Student's t test.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2211794&req=5

fig3: IgE-mediated IL-6 release of WIP−/− BMMCs. IL-6 release by BMMCs. BMMCs preloaded with IgE were incubated with F(ab′)2 anti–rat Ig for 24 h. IL-6 release was determined by ELISA. Results represent mean ± SD of three experiments. Statistical analysis was performed using the Student's t test.
Mentions: To assess the role of WIP in FcεRI-mediated cytokine production, IL-6 concentration was measured in cell culture supernatants of BMMCs 24 h after stimulation. WIP−/− BMMCs secreted markedly less IL-6 than WT controls at all concentrations of cross-linker used (Fig. 3).

Bottom Line: Calcium mobilization, phosphorylation of Syk, phospholipase C-g2, and c-Jun NH2-terminal kinase were markedly decreased in WIP-deficient BMMCs.However, the kinetics of actin changes and the cell shape changes that follow FcepsilonRI signaling were altered in WIP-deficient BMMCs.These results suggest that WIP regulates FcepsilonRI-mediated mast cell activation by regulating Syk levels and actin cytoskeleton rearrangement.

View Article: PubMed Central - PubMed

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

ABSTRACT
Wiskott-Aldrich syndrome protein-interacting protein (WIP) stabilizes actin filaments and is important for immunoreceptor-mediated signal transduction leading to actin cytoskeleton rearrangement in T and B cells. Here we report a role for WIP in signaling pathways downstream of the high affinity receptor for immunoglobulin (Ig)E (FcepsilonRI) in mast cells. WIP-deficient bone marrow-derived mast cells (BMMCs) were impaired in their capacity to degranulate and secrete interleukin 6 after FcepsilonRI ligation. Calcium mobilization, phosphorylation of Syk, phospholipase C-g2, and c-Jun NH2-terminal kinase were markedly decreased in WIP-deficient BMMCs. WIP was found to associate with Syk after FcepsilonRI ligation and to inhibit Syk degradation as evidenced by markedly diminished Syk levels in WIP-deficient BMMCs. WIP-deficient BMMCs exhibited no apparent defect in their subcortical actin network and were normal in their ability to form protrusions when exposed to an IgE-coated surface. However, the kinetics of actin changes and the cell shape changes that follow FcepsilonRI signaling were altered in WIP-deficient BMMCs. These results suggest that WIP regulates FcepsilonRI-mediated mast cell activation by regulating Syk levels and actin cytoskeleton rearrangement.

Show MeSH
Related in: MedlinePlus