Essential role for the p110 delta phosphoinositide 3-kinase in the allergic response

Article

关键词: FC-EPSILON-RI;    INCREASED INSULIN SENSITIVITY;    MAST-CELL ACTIVATION;    MICE LACKING;    P85-ALPHA SUBUNIT;    P110 DELTA;    KIT;    DIFFERENTIATION;    HYPOGLYCEMIA;    SURVIVAL;   

DOI  :  10.1038/nature02991

来源: SCIE

【 摘 要 】

Inflammatory substances released by mast cells induce and maintain the allergic response(1,2). Mast cell differentiation and activation are regulated, respectively, by stem cell factor (SCF; also known as Kit ligand) and by allergen in complex with allergen-specific immunoglobulin E (IgE)(2,3). Activated SCF receptors and high-affinity receptors for IgE (FcepsilonRI) engage phosphoinositide 3-kinases (PI(3)Ks) to generate intracellular lipid second messenger signals(2-5). Here, we report that genetic or pharmacological inactivation of the p110delta isoform of PI(3) K in mast cells leads to defective SCF-mediated in vitro proliferation, adhesion and migration, and to impaired allergen-IgE-induced degranulation and cytokine release. Inactivation of p110delta protects mice against anaphylactic allergic responses. These results identify p110delta as a new target for therapeutic intervention in allergy and mast-cell-related pathologies.

【 授权许可】

Free