Essential role for the p110δ phosphoinositide 3-kinase in the allergic response

被引：336

作者：

Ali, K

Bilancio, A

Thomas, M

Pearce, W

Gilfillan, AM

Tkaczyk, C

Kuehn, N

Gray, A

Giddings, J

Peskett, E

Fox, R

Bruce, I

Walker, C

Sawyer, C

Okkenhaug, K

Finan, P

Vanhaesebroeck, B

机构：

[1] Ludwig Inst Canc Res, London W1W 7BS, England

[2] UCL, Dept Biochem & Mol Biol, London WC1E 6BT, England

[3] Novartis Inst Biomed Res, Horsham RH12 5AB, W Sussex, England

[4] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA

[5] Frimorfo, CH-1705 Fribourg, Switzerland

[6] Univ Dundee, Dept Biochem, Dundee DD1 5EH, Scotland

来源：

NATURE | 2004年 / 431卷 / 7011期

基金：

英国生物技术与生命科学研究理事会;

关键词：

D O I：

10.1038/nature02991

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

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.

引用

页码：1007 / 1011

页数：5

共 30 条

[11] The high-affinity IgE receptor (FcεRI):: From physiology to pathology [J].