PRIMING OF HUMAN NEUTROPHIL SUPEROXIDE GENERATION BY TUMOR-NECROSIS-FACTOR-ALPHA IS SIGNALED BY ENHANCED PHOSPHATIDYLINOSITOL 3,4,5-TRISPHOSPHATE BUT NOT INOSITOL 1,4,5-TRISPHOSPHATE ACCUMULATION

In human neutrophils, significant agonist-stimulated superoxide anion (O-2(-)) release is observed only after exposure to a priming agent su ch as TNF alpha. We have investigated the potential for TNF alpha to m odulate N-formyl-Met-Leu-Phe (fMLP)-triggered Ins(1,4,5)P-3 and PtdIns (3,4,5)P-3 accumulation. TNP alpha pretreatment did not affect basal o r stimulated Ins(1,4,5)P-3 levels but greatly upregulated fMLP-stimula ted PtdIns(3,4,5)P-3 accumulation, in a manner that matched, both temp orally and in magnitude, the increase in O-2(-) generation implying a possible role for PtdIns(3,4,5)P-3 in signalling primed O-2(-) release . (C) 1998 Federation of European Biochemical Societies.