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

FEBS Letters

Chilvers, Edwin R²  Hawkins, Phillip T¹  Condliffe, Alison M²  Haslett, Christopher²  Stephens, Len R¹ 

[1] Department of Signalling, Babraham Institute, Babraham, Cambridge CB2 4AT, UK;Respiratory Medicine Unit, Department of Medicine (RIE), Rayne Laboratory, University of Edinburgh, Teviot Place, Edinburgh EH8 9AG, UK

关键词: Neutrophil;    Tumor necrosis factor;    Phosphoinositide 3-hydroxykinase;    TNFα;    tumour necrosis factor-α;    Ins(1;    4;    5)P3;    inositol 1;    4;    5-trisphosphate;    PtdIns4P;    phosphatidylinositol 4-phosphate;    PtdIns(4;    5)P2;    phosphatidylinositol 4;    5-bisphosphate;    PtdIns(3;    4;    5)P3;    phosphatidylinositol 3;    4;    5-trisphosphate;    fMLP;    N-formyl-Met-Leu-Phe;    GM-CSF;    granulocyte-macrophage colony-stimulating factor;    PI3K;    phosphoinositide 3-hydroxykinase;    PIC;    phosphoinositide-specific phospholipase C;   

DOI  :  10.1016/S0014-5793(98)01358-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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)P₃ and PtdIns(3,4,5)P₃ accumulation. TNFα 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 O⁻ ₂ generation implying a possible role for PtdIns(3,4,5)P₃ in signalling primed O⁻ ₂ release.

【 授权许可】

Unknown