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

• Published in: FEBS letters 1998-11, Vol.439 (1), p.147-151
• Main Authors: Condliffe, Alison M, Hawkins, Phillip T, Stephens, Len R, Haslett, Christopher, Chilvers, Edwin R
• Format: Article
• Language: English
• Subjects: fMLP, N-formyl-Met-Leu-Phe; GM-CSF, granulocyte-macrophage colony-stimulating factor; Humans; Inositol 1,4,5-Trisphosphate - metabolism; Ins(1,4,5)P3, inositol 1,4,5-trisphosphate; N-Formylmethionine Leucyl-Phenylalanine - metabolism; N-Formylmethionine Leucyl-Phenylalanine - pharmacology; Neutrophil; Neutrophils - metabolism; Phosphatidylinositol 3-Kinases - metabolism; Phosphatidylinositol Phosphates - metabolism; Phosphoinositide 3-hydroxykinase; Phosphorus Radioisotopes; PI3K, phosphoinositide 3-hydroxykinase; PIC, phosphoinositide-specific phospholipase C; PtdIns(3,4,5)P3, phosphatidylinositol 3,4,5-trisphosphate; PtdIns(4,5)P2, phosphatidylinositol 4,5-bisphosphate; PtdIns4P, phosphatidylinositol 4-phosphate; Signal Transduction; Superoxides - metabolism; TNFα, tumour necrosis factor-α; Transforming Growth Factor alpha - metabolism; Tumor necrosis factor
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(98)01358-1

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)P 3 and PtdIns(3,4,5)P 3 accumulation. TNFα 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 − 2 generation implying a possible role for PtdIns(3,4,5)P 3 in signalling primed O − 2 release.