Bowlin T L, McKown B J, Babcock G F, Sunkara P S
Cell Immunol. 1987 May;106(2):420-7. doi: 10.1016/0008-8749(87)90184-5.
The objective of the present investigation was to define a more precise role for intracellular polyamine biosynthesis with respect to specific inducible events which regulate lymphocyte mitogenesis. In this regard, we have examined the effect of polyamine depletion on interleukin 2 (IL-2) production, receptor expression, and responsiveness in Con A stimulated mononuclear leukocytes (MNL). Polyamine depletion was achieved utilizing the specific irreversible inhibitor of ornithine decarboxylase (ODC), DL-alpha-difluoromethylornithine (DFMO). Polyamine depletion of MNL augmented detectable levels of Con A-induced IL-2 activity. In contrast, the ability of polyamine depleted MNL to respond to saturating levels of IL-2 (100 U/ml) following 72 or 96 hr of Con A stimulation was reduced 100 and 81%, respectively. Nonetheless, polyamine depletion did not impair the induction of IL-2 receptor expression. High-affinity IL-2 receptor density in the polyamine depleted population was greater than control cells late in culture (96 hr). The expression of high-affinity IL-2 receptors did not correlate with an ability to respond to IL-2 in the polyamine depleted population. The results of this study demonstrate for the first time that intracellular polyamine biosynthesis is required for IL-2 responsiveness during a primary mitogenic lymphocyte response.
本研究的目的是确定细胞内多胺生物合成在调节淋巴细胞有丝分裂的特定诱导事件方面更精确的作用。在这方面，我们研究了多胺耗竭对伴刀豆球蛋白A（Con A）刺激的单个核白细胞（MNL）中白细胞介素2（IL-2）产生、受体表达和反应性的影响。使用鸟氨酸脱羧酶（ODC）的特异性不可逆抑制剂DL-α-二氟甲基鸟氨酸（DFMO）实现多胺耗竭。MNL的多胺耗竭增加了Con A诱导的IL-2活性的可检测水平。相反，在Con A刺激72或96小时后，多胺耗竭的MNL对饱和水平的IL-2（100 U/ml）作出反应的能力分别降低了100%和81%。尽管如此，多胺耗竭并未损害IL-2受体表达的诱导。在培养后期（96小时），多胺耗竭群体中的高亲和力IL-2受体密度高于对照细胞。在多胺耗竭群体中，高亲和力IL-2受体的表达与对IL-2作出反应的能力无关。本研究结果首次证明，在原发性有丝分裂淋巴细胞反应过程中，细胞内多胺生物合成是IL-2反应性所必需的。
