McDonald P P, Pouliot M, Borgeat P
Centre de recherche en Inflammation, immunologie et rhumatologie, Centre hospitalier de l'Université Laval, Ste-Foy, Québec, Canada.
J Lipid Mediat. 1993 Mar-Apr;6(1-3):59-67.
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.
我们研究了粒细胞巨噬细胞集落刺激因子（GM-CSF）对人中性粒细胞白三烯（LT）生物合成途径中5-脂氧合酶（5-LO）成分的影响，以便更好地理解细胞因子引发LT合成的机制。我们发现，通过使用外源性底物测定，GM-CSF增加了血小板活化因子（PAF）、N-甲酰甲硫氨酰亮氨酰苯丙氨酸（fMLP）、C5a、白三烯B4（LTB4）、白细胞介素-8（IL-8）和钙离子载体A23187引发的5-LO活化。观察到GM-CSF对5-LO活化和LT合成的引发动力学之间存在密切相关性；此外，当细胞在与GM-CSF孵育之前暴露于蛋白质合成抑制剂环己酰亚胺（CX）或转录抑制剂放线菌素D（AD）时，细胞因子对5-LO活化和LT合成的影响均被抑制。这些结果增加了一种可能性，即GM-CSF对LT合成的引发可能涉及细胞因子对5-LO蛋白质合成和基因表达的影响。
