Central role for G protein-coupled phosphoinositide 3-kinase gamma in inflammation |
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Authors: | Hirsch E Katanaev V L Garlanda C Azzolino O Pirola L Silengo L Sozzani S Mantovani A Altruda F Wymann M P |
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Institution: | Department of Genetics, Biology and Biochemistry, University of Torino, Turin, Italy. |
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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. |
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