Bomalaski J S, Freundlich B, Steiner S, Clark M A
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia.
J Leukoc Biol. 1988 Jul;44(1):51-7. doi: 10.1002/jlb.44.1.51.
The human monocyte cell line, U937, can be induced to terminally differentiate into macrophage-like cells when treated with gamma-interferon. However, if these cells were treated with gamma-interferon and esculetin, an inhibitor of the lipoxygenase pathway, or BW755C, an inhibitor of both the lipoxygenase and the cyclooxygenase pathways, a marked inhibition in cellular differentiation occurred. In contrast, inhibitors of only the cyclooxygenase pathway had no effect on differentiation. These studies suggest a role for lipoxygenase products of arachidonic acid in the differentiation of the human U937 cell line. Arachidonic acid utilized in the production of eicosanoids is derived from phospholipids by the action of phospholipase A2 and phospholipase C. When U937 cells were cultured in medium supplemented with gamma-interferon, there was a striking increase in the level of phosphatidylcholine and phosphatidylethanolamine-specific phospholipase A2 activities and phosphatidylinositol-specific phospholipase C activity as compared to control cells. More ever, although there was not a significant difference in the incorporation of labeled arachidonic acid or linoleic acid into the major phospholipids of differentiated U937 cells as compared to undifferentiated control cells, there was a marked increase in the relative amount of the labeled arachidonic acid released from the differentiated cells as lipoxygenase products compared to cyclooxygenase products. These data suggest that lipoxygenase products may be essential in the differentiation process of U937 cells and that enhanced phospholipase enzyme activities that occur during differentiation help explain how arachidonic acid becomes available to form lipoxygenase products.
人单核细胞系U937在用γ-干扰素处理时可被诱导终末分化为巨噬细胞样细胞。然而，如果用γ-干扰素以及脂氧合酶途径的抑制剂七叶亭或脂氧合酶和环氧化酶途径的双重抑制剂BW755C处理这些细胞，细胞分化会受到显著抑制。相比之下，仅抑制环氧化酶途径的抑制剂对分化没有影响。这些研究表明花生四烯酸的脂氧合酶产物在人U937细胞系的分化中发挥作用。用于生成类花生酸的花生四烯酸是通过磷脂酶A2和磷脂酶C的作用从磷脂衍生而来的。当U937细胞在添加了γ-干扰素的培养基中培养时，与对照细胞相比，磷脂酰胆碱和磷脂酰乙醇胺特异性磷脂酶A2活性以及磷脂酰肌醇特异性磷脂酶C活性水平显著增加。此外，尽管与未分化的对照细胞相比，标记的花生四烯酸或亚油酸掺入分化的U937细胞主要磷脂中的量没有显著差异，但与环氧化酶产物相比，作为脂氧合酶产物从分化细胞中释放的标记花生四烯酸的相对量显著增加。这些数据表明脂氧合酶产物可能在U937细胞的分化过程中至关重要，并且分化过程中增强的磷脂酶活性有助于解释花生四烯酸如何用于形成脂氧合酶产物。
