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  • Title: Enhancement by GM-CSF of agonist-induced 5-lipoxygenase activation in human neutrophils involves protein synthesis and gene transcription.
    Author: McDonald PP, Pouliot M, Borgeat P.
    Journal: J Lipid Mediat; 1993; 6(1-3):59-67. PubMed ID: 8358016.
    Abstract:
    We investigated the effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) on the 5-lipoxygenase (5-LO) component of the leukotriene (LT) biosynthetic pathway of human neutrophils, in order to better understand the mechanism whereby the cytokine primes for LT synthesis. We found that GM-CSF increased 5-LO activation elicited by platelet-activating factor (PAF), N-formyl-methionyl-leucyl-phenylalanine (fMLP), C5a, LTB4, IL-8 and calcium ionophore A23187, as determined by using an exogenous substrate. A close correlation was observed between the priming kinetics of GM-CSF on 5-LO activation and on LT synthesis; moreover, the effects of the cytokine on both 5-LO activation and LT synthesis were inhibited when the cells had been exposed to either the protein synthesis inhibitor, cycloheximide (CX), or the transcription inhibitor, actinomycin D (AD), prior to incubation with GM-CSF. These results raise the possibility that the priming by GM-CSF of LT synthesis may involve an effect of the cytokine on 5-LO protein synthesis and gene expression.
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