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Regulation of Mast Cell Responses by Rgs13
Author(s) -
Bansal Geetanjali,
Xie Zhihui,
Gant Vonni,
Druey Kirk
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a255-b
Subject(s) - degranulation , immunoglobulin e , mast cell , immunology , receptor , immunocytochemistry , microbiology and biotechnology , chemistry , biology , antibody , endocrinology , biochemistry
Mast cells (MCs) have important functions in allergic disease and innate immunity mediated principally by IgE‐crosslinking of a high affinity receptor. Regulators of G Protein Signaling (RGS) proteins are known to inhibit many GPCR‐mediated responses. Rgs1, Rgs8, Rgs13 and Rgs18 mRNA was identified in murine bone marrow‐derived MCs (BMMCs) by RT‐PCR using degenerate primers encompassing the RGS box. Using real time PCR, we found that Fc epsilon RI aggregation or adenosine increased Rgs13 levels, while eotaxin decreased Rgs13 expression. Neither SCF nor C5a significantly affected Rgs13 levels. Immunocytochemistry revealed cytoplasmic localization of endogenous Rgs13 in BMMCs. Rgs13−/− mice with LacZ knock‐in were generated, allowing determination of Rgs13 expression by beta‐galactosidase tissue staining. We identified beta‐gal+/toluidine‐blue+ MCs in skin, conjunctiva, and gastrointestinal tract in Rgs13−/− mice. IgE‐Ag stimulation produced enhanced degranulation in Rgs13‐deficient MCs. IgE‐evoked calcium flux was also increased in Rgs13−/− BMMCs. In addition, Rgs13−/− mice exhibited amplified IgE‐mediated systemic and passive cutaneous anaphylactic responses. These data suggest that Rgs13 normally suppresses IgE‐dependent allergic reactions mediated by mast cells. The work was funded by Division of Intramural Research, NIAID/NIH.