Differential effect on polyamine metabolism in mitogen- and superantigen-activated human T-cells.
Polyamines are important for regulation of lymphocyte differentiation and proliferation. Mitogens induce synthesis of ornithine decarboxylase (ODC), the rate limiting enzyme in polyamine biosynthesis. Since mitogens stimulate T-cells by non-physiological routes, the role of polyamine metabolism in T-cell receptor (TCR)-mediated T-cell activation has not been adequately evaluated. The effect of phytohemagglutinin (PHA) and staphylococcal enterotoxin B (SEB) on T-cell ODC and polyamine synthesis was compared. ODC activity was 6-11-fold higher in PHA compared to SEB stimulated T-cells. These differences were not attributed to differences in the magnitude of T-cell proliferation. Kinetics of ODC and polyamine synthesis were also different in PHA- and SEB-stimulated T-cells. In PHA-stimulated cells ODC levels and the induction of putrescine and spermidine synthesis peaked 6 h prior to peak IL-2 production, while in SEB-stimulated cells, ODC levels and polyamine synthesis peaked 6-12 h after IL-2 production. Differences in the temporal relationship between IL-2 production and polyamine induction in mitogen- versus superantigen-stimulated cells may account for the significant inhibition of the proliferative response by alpha-difluoromethylornithine following PHA but not SEB stimulation. Polyamine metabolism is regulated differently in T-cells stimulated via TCR engagement than with polyclonal mitogens.
Langkamp-Henken
B
B
Department of Microbiology and Immunology, University of Tennessee-Memphis, Memphis, TN 38104, USA.
Johnson
L R
LR
Viar
M J
MJ
Geller
A M
AM
Kotb
M
M
D000518:Eflornithine; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008934:Mitogens / Q000494:pharmacology*; D009955:Ornithine Decarboxylase / Q000378:metabolism; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines / Q000378:metabolism*; D011700:Putrescine / Q000032:analysis; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D013095:Spermidine / Q000032:analysis; D018089:Superantigens / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism
D007376:Interleukin-2; D008934:Mitogens; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines; D015375:Receptors, Interleukin-2; D018089:Superantigens; D009955:Ornithine Decarboxylase; D013095:Spermidine; D011700:Putrescine; D000518:Eflornithine