Priming of human neutrophil superoxide generation by tumour necrosis factor‐α is signalled by enhanced phosphatidylinositol 3,4,5‐trisphosphate but not inositol 1,4,5‐trisphosphate accumulation

Abstract
In human neutrophils, significant agonist-stimulated superoxide anion (O 2) release is observed only after exposure to a priming agent such as TNFα. We have investigated the potential for TNFα to modulate N-formyl-Met-Leu-Phe (fMLP)-triggered Ins(1,4,5)P3 and PtdIns(3,4,5)P3 accumulation. TNFα pretreatment did not affect basal or stimulated Ins(1,4,5)P3 levels but greatly upregulated fMLP-stimulated PtdIns(3,4,5)P3 accumulation, in a manner that matched, both temporally and in magnitude, the increase in O 2 generation implying a possible role for PtdIns(3,4,5)P3 in signalling primed O 2 release.