Co-operation of phosphatidylinositol transfer protein with phosphoinositide 3-kinase γ in the formylmethionyl-leucylphenylalanine-dependent production of phosphatidylinositol 3,4,5-trisphosphate in human neutrophils

摘要

pPhosphoinositide 3-kinase (PI3K) and its product phosphatidylinositol 3,4,5-trisphosphate (PIPsub3/sub) play an essential role in the regulation of neutrophil functions by the chemoattractant formylmethionyl-leucylphenylalanine (FMLP). Here we show that permeabilization of human neutrophils leads to loss of cytosolic components, including PI3Kγ, and causes the loss of FMLP-dependent production of PIPsub3/sub. FMLP-sensitive synthesis of PIPsub3/sub could be restored by reconstitution of permeabilized neutrophils with recombinant PI3Kγ. Admixture of recombinant phosphatidylinositol transfer protein (PITP) to the reconstitution cocktail produced a further increase of PIPsub3/sub synthesis, whereas pertussis toxin suppressed the FMLP-dependent production of PIPsub3/sub. We conclude that FMLP-sensitive PIPsub3/sub formation in human neutrophils involves the FMLP receptor, heterotrimeric G-proteins of the Gsubi/sub type, PI3Kγ and PITP./p