title: Phosphoinositide 3-kinase gamma is an essential amplifier of mast cell function.
abstract: Mast cells are key regulators in allergy and inflammation, and release histamine upon clustering of their IgE receptors. Here we demonstrate that murine mast cell responses are exacerbated in vitro and in vivo by autocrine signals through G protein-coupled receptors (GPCRs) and require functional phosphoinositide 3-kinase gamma (PI3Kgamma). Adenosine, acting through the A(3) adenosine receptor (A(3)AR) as well as other agonists of G(alphai)-coupled GPCRs, transiently increased PtdIns(3,4,5)P(3) exclusively via PI3Kgamma. PI3Kgamma-derived PtdIns(3,4,5)P(3) was instrumental for initiating a sustained influx of external Ca(2+) and degranulation. Mice lacking PI3Kgamma did not form edema after intradermal injection of adenosine and when challenged by passive systemic anaphylaxis. PI3Kgamma thus relays inflammatory signals through various G(i)-coupled receptors and is central to mast cell function.
authors.affiliation: Institute of Biochemistry, Department of Medicine, University of Fribourg, Rue du Musée 5, CH-1700 Fribourg, Switzerland.
authors.forename: Muriel
authors.initials: M
authors.lastname: Laffargue
authors.forename: Ronan
authors.initials: R
authors.lastname: Calvez
authors.forename: Peter
authors.initials: P
authors.lastname: Finan
authors.forename: Alexandre
authors.initials: A
authors.lastname: Trifilieff
authors.forename: Maryse
authors.initials: M
authors.lastname: Barbier
authors.forename: Fiorella
authors.initials: F
authors.lastname: Altruda
authors.forename: Emilio
authors.initials: E
authors.lastname: Hirsch
authors.forename: Matthias P
authors.initials: MP
authors.lastname: Wymann
mesh_terms: D000818:Animals; D019898:Autocrine Communication / Q000276:immunology; D015550:Cell Degranulation / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D019204:GTP-Binding Proteins / Q000502:physiology; D008407:Mast Cells / Q000276:immunology / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology
chemical_list: D011956:Receptors, Cell Surface; D019869:Phosphatidylinositol 3-Kinases; D019204:GTP-Binding Proteins