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

被引:38
作者
Condliffe, AM
Hawkins, PT
Stephens, LR
Haslett, C
Chilvers, ER
机构
[1] Univ Edinburgh, Rayne Lab, Dept Med RIE, Resp Med Unit, Edinburgh EH8 9AG, Midlothian, Scotland
[2] Babraham Inst, Dept Signalling, Cambridge CB2 4AT, England
基金
英国惠康基金;
关键词
neutrophil; tumor necrosis factor; phosphoinositide; 3-hydroxykinase;
D O I
10.1016/S0014-5793(98)01358-1
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
In human neutrophils, significant agonist-stimulated superoxide anion (O-2(-)) release is observed only after exposure to a priming agent such as TNF alpha. We have investigated the potential for TNF alpha to modulate 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 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. (C) 1998 Federation of European Biochemical Societies.
引用
收藏
页码:147 / 151
页数:5
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