PMID- 15496927
OWN - NLM
STAT- MEDLINE
DCOM- 20041126
LR  - 20201208
IS  - 1476-4687 (Electronic)
IS  - 0028-0836 (Linking)
VI  - 431
IP  - 7011
DP  - 2004 Oct 21
TI  - Essential role for the p110delta phosphoinositide 3-kinase in the allergic 
      response.
PG  - 1007-11
AB  - Inflammatory substances released by mast cells induce and maintain the allergic 
      response. 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). Activated SCF receptors and 
      high-affinity receptors for IgE (FcvarepsilonRI) engage phosphoinositide 
      3-kinases (PI(3)Ks) to generate intracellular lipid second messenger signals. 
      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.
FAU - Ali, Khaled
AU  - Ali K
AD  - Ludwig Institute for Cancer Research, 91 Riding House Street, London W1W 7BS, UK.
FAU - Bilancio, Antonio
AU  - Bilancio A
FAU - Thomas, Matthew
AU  - Thomas M
FAU - Pearce, Wayne
AU  - Pearce W
FAU - Gilfillan, Alasdair M
AU  - Gilfillan AM
FAU - Tkaczyk, Christine
AU  - Tkaczyk C
FAU - Kuehn, Nicolas
AU  - Kuehn N
FAU - Gray, Alexander
AU  - Gray A
FAU - Giddings, June
AU  - Giddings J
FAU - Peskett, Emma
AU  - Peskett E
FAU - Fox, Roy
AU  - Fox R
FAU - Bruce, Ian
AU  - Bruce I
FAU - Walker, Christoph
AU  - Walker C
FAU - Sawyer, Carol
AU  - Sawyer C
FAU - Okkenhaug, Klaus
AU  - Okkenhaug K
FAU - Finan, Peter
AU  - Finan P
FAU - Vanhaesebroeck, Bart
AU  - Vanhaesebroeck B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (Cytokines)
RN  - 0 (Interleukin-3)
RN  - 0 (Isoenzymes)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Receptors, IgE)
RN  - 0 (Stem Cell Factor)
RN  - EC 2.7.1.137 (Class I Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.1.137 (Pik3cd protein, mouse)
SB  - IM
MH  - Anaphylaxis/enzymology/immunology
MH  - Animals
MH  - Cell Adhesion/drug effects
MH  - Cell Count
MH  - Cell Degranulation/drug effects
MH  - Cell Movement/drug effects
MH  - Class I Phosphatidylinositol 3-Kinases
MH  - Cytokines/metabolism
MH  - Dermis/cytology
MH  - Genes, Essential/genetics
MH  - Humans
MH  - Hypersensitivity/*enzymology/immunology
MH  - Interleukin-3/pharmacology
MH  - Isoenzymes/antagonists & inhibitors/genetics/metabolism
MH  - Mast Cells/cytology/*enzymology/immunology/metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Phosphatidylinositol 3-Kinases/genetics/*metabolism
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Receptors, IgE/immunology
MH  - Second Messenger Systems/physiology
MH  - Stem Cell Factor/pharmacology
EDAT- 2004/10/22 09:00
MHDA- 2004/12/16 09:00
CRDT- 2004/10/22 09:00
PHST- 2004/07/16 00:00 [received]
PHST- 2004/09/02 00:00 [accepted]
PHST- 2004/10/22 09:00 [pubmed]
PHST- 2004/12/16 09:00 [medline]
PHST- 2004/10/22 09:00 [entrez]
AID - nature02991 [pii]
AID - 10.1038/nature02991 [doi]
PST - ppublish
SO  - Nature. 2004 Oct 21;431(7011):1007-11. doi: 10.1038/nature02991.