title: Phagocytosis of bone marrow derived macrophages is controlled by phosphoinositide 3-kinase γ.
abstract: Due to their ability to phagocytise invading microbes macrophages play a key role in the innate and acquired immune system. In this article the role of phosphoinositide 3-kinase gamma (PI3Kγ) for phagocytosis was studied in bone marrow derived macrophages (BMDM). By using genetic and pharmacological approaches our data clearly demonstrate PI3Kγ is acting as a mediator of macrophage phagocytosis. Phagocytosis of LPS activated BMDM was reduced in PI3Kγ depleted primary BMDM or macrophage cell line J774. Depletion of other class I phosphoinositide 3-kinases did not alter phagocytic activity. Partial reduction of the phagocytic index of BMDM expressing kinase inactive PI3Kγ indicate a lipid-kinase independent role of the PI3Kγ protein. Since inhibition of PI3Kγ interaction partner phosphodiesterase PDE3B reduced BMDM phagocytosis and PI3Kγ knock out super stimulated cAMP level, our data reveal that PI3Kγ protein mediated suppression of cAMP signalling is a critical for efficient phagocytosis of macrophages.
authors.affiliation: Institute of Molecular Cell Biology, Center for Molecular Biomedicine (CMB), Jena University Hospital, Hans-Knöll-Straße 2, Jena, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Kresinsky
authors.affiliation: Institute of Molecular Cell Biology, Center for Molecular Biomedicine (CMB), Jena University Hospital, Hans-Knöll-Straße 2, Jena, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Schneble
authors.affiliation: Institute of Molecular Cell Biology, Center for Molecular Biomedicine (CMB), Jena University Hospital, Hans-Knöll-Straße 2, Jena, Germany.
authors.forename: Caroline
authors.initials: C
authors.lastname: Schmidt
authors.affiliation: Institute of Molecular Cell Biology, Center for Molecular Biomedicine (CMB), Jena University Hospital, Hans-Knöll-Straße 2, Jena, Germany.
authors.forename: Adrian
authors.initials: A
authors.lastname: Frister
authors.affiliation: Institute of Molecular Cell Biology, Center for Molecular Biomedicine (CMB), Jena University Hospital, Hans-Knöll-Straße 2, Jena, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Bauer
authors.affiliation: Institute of Molecular Cell Biology, Center for Molecular Biomedicine (CMB), Jena University Hospital, Hans-Knöll-Straße 2, Jena, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Wetzker
authors.affiliation: Institute of Molecular Cell Biology, Center for Molecular Biomedicine (CMB), Jena University Hospital, Hans-Knöll-Straße 2, Jena, Germany. Electronic address: joerg.mueller2@med.uni-jena.de.
authors.forename: Jörg P
authors.initials: JP
authors.lastname: Müller
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000378:metabolism* / Q000502:physiology*; D002460:Cell Line; D008264:Macrophages / Q000378:metabolism* / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D010587:Phagocytosis / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D019869:Phosphatidylinositol 3-Kinases
keywords: Knock out; Lipid-kinase; PI3Kγ; Phosphodiesterase; Signalling; cAMP