Wiederhold M D, Ondrey F, Anderson K M, Braun D, Harris J
Department of Internal Medicine, Rush Medical College, Chicago, Ill.
Clin Physiol Biochem. 1988;6(1):21-8.
Interferons induce morphological, biochemical and functional alterations in monocyte macrophage and myeloid cell lines. We studied the effect of 3 days incubation with gamma-interferon from human buffy coats on the global synthesis of arachidonic acid metabolites by U937 cells. Interferon-induced morphologic changes including cytoplasmic and nuclear changes and the appearance of multiple lysosomal-like granules consistent with cellular differentiation were observed by electron microscopy. The labeling of phosphatidylserine, phosphatidylcholine and phosphatidylethanolamine was increased and that of phosphatidylinositol, free fatty acids as 3H-arachidonic acid and neutral lipids reduced, when interferon-treated cells were incubated with 3H-arachidonic acid. Interferon caused qualitative and quantitative changes in the synthesis of cyclooxygenase and lipoxygenase products. A23187, a calcium ionophore, and the tumor promotor, phorbol myristate acetate, greatly increased the synthesis by interferon-differentiated cells of 2 cyclooxygenase products; synthesis of lipoxygenase products was reduced. In the presence of indomethacin, 'shunting' into putative lipoxygenase products occurred. The relationship between interferon-induced morphologic and functional changes, the development of altered phospholipid and eicosanoid metabolism and the identity of these metabolites are yet to be established.
干扰素可诱导单核细胞巨噬细胞和髓样细胞系发生形态、生化及功能改变。我们研究了用人血沉棕黄层中的γ干扰素对U937细胞进行3天孵育后,其对花生四烯酸代谢产物整体合成的影响。通过电子显微镜观察到,干扰素诱导的形态学变化包括细胞质和细胞核变化以及出现多个与细胞分化一致的溶酶体样颗粒。当用³H-花生四烯酸孵育经干扰素处理的细胞时,磷脂酰丝氨酸、磷脂酰胆碱和磷脂酰乙醇胺的标记增加,而磷脂酰肌醇、作为³H-花生四烯酸的游离脂肪酸和中性脂质的标记减少。干扰素导致环氧化酶和脂氧合酶产物合成发生质和量的变化。钙离子载体A23187和肿瘤促进剂佛波酯肉豆蔻酸乙酸酯极大地增加了经干扰素分化的细胞对两种环氧化酶产物的合成;脂氧合酶产物的合成减少。在吲哚美辛存在的情况下,出现了向假定的脂氧合酶产物的“分流”。干扰素诱导的形态学和功能变化、磷脂和类二十烷酸代谢改变的发展以及这些代谢产物的身份之间的关系尚待确定。