Intracellular polyamine biosynthesis is required for interleukin 2 responsiveness during lymphocyte mitogenesis.
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.
D003208:Concanavalin A / Q000037:antagonists & inhibitors; D004247:DNA / Q000096:biosynthesis; D000518:Eflornithine / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D007376:Interleukin-2 / Q000502:physiology*; D008213:Lymphocyte Activation / Q000187:drug effects; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines / Q000096:biosynthesis*; D011971:Receptors, Immunologic / Q000502:physiology*; D015375:Receptors, Interleukin-2
D007376:Interleukin-2; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D003208:Concanavalin A; D004247:DNA; D000518:Eflornithine