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

FEBS Lett. 1998 Nov 13;439(1-2):147-51. doi: 10.1016/s0014-5793(98)01358-1.

Abstract

In human neutrophils, significant agonist-stimulated superoxide anion (O2-) 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)P3 and PtdIns(3,4,5)P3 accumulation. TNFalpha 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 O2- generation implying a possible role for PtdIns(3,4,5)P3 in signalling primed O2- release.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Inositol 1,4,5-Trisphosphate / metabolism*
  • N-Formylmethionine Leucyl-Phenylalanine / metabolism
  • N-Formylmethionine Leucyl-Phenylalanine / pharmacology
  • Neutrophils / metabolism*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphatidylinositol Phosphates / metabolism*
  • Phosphorus Radioisotopes
  • Signal Transduction
  • Superoxides / metabolism*
  • Transforming Growth Factor alpha / metabolism*

Substances

  • Phosphatidylinositol Phosphates
  • Phosphorus Radioisotopes
  • Transforming Growth Factor alpha
  • Superoxides
  • N-Formylmethionine Leucyl-Phenylalanine
  • Inositol 1,4,5-Trisphosphate
  • Phosphatidylinositol 3-Kinases