The role of SHIP in the development and activation of mouse mucosal and connective tissue mast cells

Jens Ruschmann, Frann Antignano, Vivian Lam, Kim Snyder, Connie Kim, Martha Essak, Angela Zhang, Ann Hsu An Lin, Raghuveer Singh Mali, Reuben Kapur, Gerald Krystal

Research output: Contribution to journalArticle

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Abstract

Although SHIP is a well-established suppressor of IgE plus Ag-induced degranulation and cytokine production in bone marrow-derived mast cells (BMMCs), little is known about its role in connective tissue (CTMCs) or mucosal (MMCs) mast cells. In this study, we compared SHIP's role in the development as well as the IgE plus Ag and TLR-induced activation of CTMCs, MMCs, and BMMCs and found that SHIP delays the maturation of all three mast cell subsets and, surprisingly, that it is a positive regulator of IgE-induced BMMC survival. We also found that SHIP represses IgE plus Ag-induced degranulation of all three mast cell subsets and that TLR agonists do not trigger their degranulation, whether SHIP is present or not, nor do they enhance IgE plus Ag-induced degranulation. In terms of cytokine production, we found that in MMCs and BMMCs, which are poor producers of TLR-induced cytokines, SHIP is a potent negative regulator of IgE plus Ag-induced IL-6 and TNF-α production. Surprisingly, however, in splenic or peritoneal derived CTMCs, which are poor producers of IgE plus Ag-induced cytokines, SHIP is a potent positive regulator of TLR-induced cytokine production. Lastly, cell signaling and cytokine production studies with and without LY294002, wortmannin, and PI3Kα inhibitor-2, as well as with PI3K p85α -/- BMMCs and CTMCs, are consistent with SHIP positively regulating TLR-induced cytokine production via an adaptor-mediated pathway while negatively regulating IgE plus Ag-induced cytokine production by repressing the PI3K pathway.

Original languageEnglish
Pages (from-to)3839-3850
Number of pages12
JournalJournal of Immunology
Volume188
Issue number8
DOIs
StatePublished - Apr 15 2012

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Connective Tissue Cells
Mast Cells
Immunoglobulin E
Mucous Membrane
Cytokines
Bone Marrow
Phosphatidylinositol 3-Kinases
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Connective Tissue
Interleukin-6
Cell Survival

ASJC Scopus subject areas

  • Immunology

Cite this

Ruschmann, J., Antignano, F., Lam, V., Snyder, K., Kim, C., Essak, M., ... Krystal, G. (2012). The role of SHIP in the development and activation of mouse mucosal and connective tissue mast cells. Journal of Immunology, 188(8), 3839-3850. https://doi.org/10.4049/jimmunol.1003875

The role of SHIP in the development and activation of mouse mucosal and connective tissue mast cells. / Ruschmann, Jens; Antignano, Frann; Lam, Vivian; Snyder, Kim; Kim, Connie; Essak, Martha; Zhang, Angela; Lin, Ann Hsu An; Mali, Raghuveer Singh; Kapur, Reuben; Krystal, Gerald.

In: Journal of Immunology, Vol. 188, No. 8, 15.04.2012, p. 3839-3850.

Research output: Contribution to journalArticle

Ruschmann, J, Antignano, F, Lam, V, Snyder, K, Kim, C, Essak, M, Zhang, A, Lin, AHA, Mali, RS, Kapur, R & Krystal, G 2012, 'The role of SHIP in the development and activation of mouse mucosal and connective tissue mast cells', Journal of Immunology, vol. 188, no. 8, pp. 3839-3850. https://doi.org/10.4049/jimmunol.1003875
Ruschmann, Jens ; Antignano, Frann ; Lam, Vivian ; Snyder, Kim ; Kim, Connie ; Essak, Martha ; Zhang, Angela ; Lin, Ann Hsu An ; Mali, Raghuveer Singh ; Kapur, Reuben ; Krystal, Gerald. / The role of SHIP in the development and activation of mouse mucosal and connective tissue mast cells. In: Journal of Immunology. 2012 ; Vol. 188, No. 8. pp. 3839-3850.
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AU - Kapur, Reuben

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