Granulocyte/macrophage colony-stimulating factor affects myo-inositol metabolism in a novel manner. Implications for its priming action on human neutrophils.
Biochem J
; 286 ( Pt 2): 535-40, 1992 Sep 01.
Article
en En
| MEDLINE
| ID: mdl-1530586
ABSTRACT
Little is known about the signal transduction processes involved in the priming action of granulocyte/macrophage colony-stimulating factor (GM-CSF) on neutrophils. This study has used myo-[3H]inositol-labelled human neutrophils to determine whether preincubation with GM-CSF influences myo-inositol (Ins) metabolism in control cells, or in cells stimulated with the bacterial chemoattractant N-formyl-methionyl-leucyl-phenylalanine (fMetLeuPhe). GM-CSF pretreatment did not influence the total cellular 3H radioactivity content, demonstrating that the cytokine had no effect on Ins uptake. However, neutrophils pretreated with GM-CSF showed a dramatic 25-40% fall in the free [3H]Ins content of the cell, which was almost quantitatively recovered in a 2-4-fold increase in radioactivity within PtdIns. The remainder of the 3H radioactivity was found proportionately distributed throughout all other [3H]Ins-containing metabolites. Interestingly, in comparison with controls, the GM-CSF-stimulated increases in [3H]polyphosphoinositide (including 3-phosphorylated lipids) and [3H]Ins polyphosphate contents were consistently higher than that observed with PtdIns. This observation suggests that GM-CSF influences the hormone-sensitive pool of PtdIns, possibly through the activation of a PtdIns synthase which is rate-limiting to subsequent metabolic pathways. This is the first report of an action of GM-CSF on Ins metabolism, and highlights the conversion of Ins to PtdIns as a key regulatory metabolic step.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Factor Estimulante de Colonias de Granulocitos y Macrófagos
/
Inositol
/
Neutrófilos
Límite:
Humans
Idioma:
En
Revista:
Biochem J
Año:
1992
Tipo del documento:
Article
País de afiliación:
Reino Unido