SHIP is a repressor of mast cell hyperplasia, cytokine production, and allergic inflammation in vivo (139.12)
| Autor: | David James Haddon, Frann Antignano, Michael R Hughes, Marie-Renée Blanchet, Lori Zbytnuik, Gerald Krystal, Kelly Marshall McNagny |
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| Rok vydání: | 2009 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 182:139.12-139.12 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.182.supp.139.12 |
| Popis: | Src homology 2-containing inositol 5'-phosphatase (SHIP) inhibits immune receptor signaling through hydrolysis of the phosphatidylinositol-3 kinase (PI3K) product PI-3,4,5-P3, forming PI-3,4-P2. SHIP represses FcεRI- and cytokine-mediated mast cell activation in vitro, but little is known regarding the function of SHIP in mast cells in vivo, or the susceptibility of Ship-/- mice to mast cell-associated diseases. In this study, we found that Ship-/- mice have systemic mast cell hyperplasia, increased serum levels of IL-6, TNF, and IL-5, and heightened anaphylactic response. Further, by reconstituting mast cell-deficient mice with Ship+/+ or Ship-/- mast cells, we found that the above defects were due to loss of SHIP in mast cells. Additionally, we found that loss of SHIP in mast cells alone resulted in increased allergic asthma pathology. In summary, our data show that SHIP represses allergic inflammation and mast cell hyperplasia in vivo, and that SHIP exerts these effects specifically in mast cells. |
| Databáze: | OpenAIRE |
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