Priming of human neutrophil superoxide generation by tumour necrosis factor#x2010;alpha; is signalled by enhanced phosphatidylinositol 3,4,5#x2010;trisphosphate but not inositol 1,4,5#x2010;trisphosphate accumulation

摘要

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