Article: article from journal or magazin.
Central role for G protein-coupled phosphoinositide 3-kinase gamma in inflammation.
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.
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, Neutrophils/physiology, Peritonitis/enzymology, Peritonitis/immunology, 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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