Valone F H, Epstein L B
Department of Medicine, University of California, San Francisco.
J Immunol. 1988 Dec 1;141(11):3945-50.
The capacity of IL-1-beta, TNF, and IFN-gamma to stimulate platelet-activating factor (PAF) synthesis by human monocytes is examined in our report. All three cytokines induced PAF synthesis in a novel biphasic pattern with peaks of PAF synthesis 1 to 2 and 6 to 8 h after stimulation of the monocytes. In contrast, calcium ionophore A23187 elicited a single peak of early PAF synthesis. PAF in the early peak was largely retained intracellularly whereas PAF in the late peak was largely released into culture fluids. Combinations of cytokines were subadditive or antagonistic in inducing PAF synthesis. Cycloheximide inhibited the late peak of PAF synthesis indicating that protein synthesis is required for synthesis of the phospholipid PAF. Specific antibodies to TNF or IL-1-beta inhibited the late peak of PAF synthesis induced by IFN-gamma indicating that late PAF synthesis is dependent on cytokine synthesis. The quantities of PAF produced by cytokine-activated monocytes are sufficient to activate human monocytes. Thus, these studies suggest that PAF may mediate in part monocyte activation by cytokines.
我们的报告中检测了白细胞介素-1β（IL-1-β）、肿瘤坏死因子（TNF）和γ干扰素（IFN-γ）刺激人单核细胞合成血小板活化因子（PAF）的能力。所有这三种细胞因子均以一种新的双相模式诱导PAF合成，在刺激单核细胞后1至2小时和6至8小时出现PAF合成高峰。相比之下，钙离子载体A23187引发早期PAF合成的单一高峰。早期高峰中的PAF大部分保留在细胞内，而晚期高峰中的PAF大部分释放到培养液中。细胞因子组合在诱导PAF合成方面具有亚加性或拮抗性。放线菌酮抑制PAF合成的晚期高峰，表明磷脂PAF的合成需要蛋白质合成。针对TNF或IL-1-β的特异性抗体抑制IFN-γ诱导的PAF合成晚期高峰，表明晚期PAF合成依赖于细胞因子合成。细胞因子激活的单核细胞产生的PAF量足以激活人单核细胞。因此，这些研究表明PAF可能部分介导细胞因子对单核细胞的激活作用。
