Central role for G protein-coupled phosphoinositide 3-kinase gamma in inflammation.

Abstract	Phosphoinositide 3-kinase (PI3K) activity is crucial for leukocyte function, but the roles of the four receptor-activated isoforms are unclear. Mice lacking heterotrimeric guanine nucleotide-binding protein (G protein)-coupled PI3Kgamma were viable and had fully differentiated neutrophils and macrophages. Chemoattractant-stimulated PI3Kgamma-/- neutrophils did not produce phosphatidylinositol 3,4,5-trisphosphate, did not activate protein kinase B, and displayed impaired respiratory burst and motility. Peritoneal PI3Kgamma-null macrophages showed a reduced migration toward a wide range of chemotactic stimuli and a severely defective accumulation in a septic peritonitis model. These results demonstrate that PI3Kgamma is a crucial signaling molecule required for macrophage accumulation in inflammation.
Authors	E Hirsch, V L Katanaev, C Garlanda, O Azzolino, L Pirola, L Silengo, S Sozzani, A Mantovani, F Altruda, M P Wymann
Journal	Science (New York, N.Y.) (Science) Vol. 287 Issue 5455 Pg. 1049-53 (Feb 11 2000) ISSN: 0036-8075 [Print] United States
PMID	10669418 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Chemotactic Factors Isoenzymes Phosphatidylinositol Phosphates Proto-Oncogene Proteins phosphatidylinositol 3,4,5-triphosphate Protein Serine-Threonine Kinases Proto-Oncogene Proteins c-akt Heterotrimeric GTP-Binding Proteins
Topics	Animals Chemotactic Factors (pharmacology) Chemotaxis Chemotaxis, Leukocyte (physiology) Enzyme Activation Gene Targeting Heterotrimeric GTP-Binding Proteins (metabolism) Isoenzymes (metabolism) Macrophages, Peritoneal (physiology) Mice Mice, Inbred C57BL Mice, Knockout Neutrophils (metabolism, physiology) Peritonitis (enzymology, immunology, pathology) Phosphatidylinositol 3-Kinases (metabolism) Phosphatidylinositol Phosphates (metabolism) Protein Serine-Threonine Kinases Proto-Oncogene Proteins (metabolism) Proto-Oncogene Proteins c-akt Respiratory Burst Signal Transduction

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