Phosphoinositide 3-kinase (PI3K) activity is crucial for Leukocyte function
, but the roles of the four receptor-activated isoforms are unclear. Mice L
acking heterotrimeric guanine nucleotide-binding protein (G protein)-couple
d PI3K gamma were viable and had fully differentiated neutrophils and macro
phages. Chemoattractant-stimulated PI3K gamma(-/-) neutrophils did not prod
uce phosphatidylinositol 3,4,5-trisphosphate, did not activate protein kina
se B, and displayed impaired respiratory burst and motility. Peritoneal PI3
K gamma-null macrophages showed a reduced migration toward a wide range of
chemotactic stimuli and a severely defective accumulation in a septic perit
onitis model. These results demonstrate that PI3K gamma is a crucial signal
ing molecule required for macrophage accumulation in inflammation.