Roles of PI3K in Neutrophil Function

Neutrophils are terminally differentiated cells that play a vital role in host defense. It has recently become evident that phospholipid regulation plays an import role in many neutrophil functions. We review the regulation of neutrophil functions such as chemotaxis, superoxide production, and phagocytosis by phosphatidylinositol-3,4,5-trisphosphate (PIP3), which is generated in neutrophils by PI3Kγ. Several lines of evidence are presented demonstrating the importance of this kinase in regulating chemotaxis, in particular the directionality of chemotactic migration. Evidence suggesting that this kinase is important for phagocytosis, especially during engulfment and the internalization of large particles, is also reviewed. Finally, it is suggested that PI3K is important for superoxide production and neutrophil priming. The common link between these seemingly diverse functions is that PI3Kγ, via its phospholipid products, appears to be providing spatial-temporal cues for the binding of actin-organizing proteins.