Central Role for G Protein-Coupled Phosphoinositide 3-Kinase γ 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 PI3Kγ were viable and had fully differentiated neutrophils and macrophages. Chemoattractant-stimulated PI3Kγ-/- neutrophils did not produce phosphatidylinositol 3,4,5-trisphosphate, did not activate protein kinase B, and displayed impaired respiratory burst and motility. Peritoneal PI3Kγ-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 PI3Kγ is a crucial signaling molecule required for macrophage accumulation in inflammation.
- Publication:
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Science
- Pub Date:
- February 2000
- DOI:
- 10.1126/science.287.5455.1049
- Bibcode:
- 2000Sci...287.1049H
- Keywords:
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- CELL BIOL