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.
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.
Condliffe
A M
AM
Department of Medicine (RIE), University of Edinburgh, UK.
Hawkins
P T
PT
Stephens
L R
LR
Haslett
C
C
Chilvers
E R
ER
D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000378:metabolism / Q000494:pharmacology; D009504:Neutrophils / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D010761:Phosphorus Radioisotopes; D015398:Signal Transduction; D013481:Superoxides / Q000378:metabolism*; D016211:Transforming Growth Factor alpha / Q000378:metabolism*
D018129:Phosphatidylinositol Phosphates; D010761:Phosphorus Radioisotopes; D016211:Transforming Growth Factor alpha; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015544:Inositol 1,4,5-Trisphosphate; D019869:Phosphatidylinositol 3-Kinases