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- Title
Central role for G protein-coupled phosphoinositide 3-kinase gamma in inflammation.
- Authors
Hirsch, E; Katanaev, V L; Garlanda, C; Azzolino, O; Pirola, L; Silengo, L; Sozzani, S; Mantovani, A; Altruda, F; Wymann, M P
- 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.
- Publication
Science (New York, N.Y.), 2000, Vol 287, Issue 5455, p1049
- ISSN
0036-8075
- Publication type
Journal Article
- DOI
10.1126/science.287.5455.1049