Kaczmarek L, Kaminska B, Messina L, Spampinato G, Arcidiacono A, Malaguarnera L, Messina A
Nencki Institute of Experimental Biology, Warsaw, Poland.
Cancer Res. 1992 Apr 1;52(7):1891-4.
The activation of polyamine biosynthesis, dependent on increased gene expression of ornithine decarboxylase, has been found to play an important role in the control of cell proliferation and differentiation. In this report it has been found that accumulation of ornithine decarboxylase mRNA also follows stimulation of human monocytes/macrophages by tumor necrosis factor. Human recombinant tumor necrosis factor (100 units/ml) also evoked an enhanced respiratory burst of macrophages. The respiratory burst response was inhibited in a dose-dependent manner with difluoromethylornithine, an inhibitor of ornithine decarboxylase, and methylglyoxal-bis(guanylhydrazone), an inhibitor of the formation of spermidine and spermine. The data presented in this paper suggest that polyamines may play a functional role in tumor necrosis factor-driven macrophage activation, and they are discussed in the context of their possible use as inhibitors of polyamine metabolism in tumor chemotherapy.
多胺生物合成的激活依赖于鸟氨酸脱羧酶基因表达的增加，已发现其在细胞增殖和分化的控制中起重要作用。在本报告中，已发现肿瘤坏死因子刺激人单核细胞/巨噬细胞后，鸟氨酸脱羧酶mRNA也会积累。人重组肿瘤坏死因子（100单位/毫升）也会引起巨噬细胞呼吸爆发增强。鸟氨酸脱羧酶抑制剂二氟甲基鸟氨酸和亚精胺及精胺形成抑制剂甲基乙二醛双（脒腙）可剂量依赖性地抑制呼吸爆发反应。本文提供的数据表明，多胺可能在肿瘤坏死因子驱动的巨噬细胞激活中发挥功能作用，并在其作为肿瘤化疗中多胺代谢抑制剂的可能用途的背景下进行了讨论。
