Polyamine oxidation down-regulates IL-2 production by human peripheral blood mononuclear cells.
Polyamine biosynthesis by mononuclear cells (MNC) appears to regulate T cell activity since 1) inhibition of polyamine biosynthesis increases IL-2 production and 2) H2O2 (a product of polyamine oxidase, PAO), suppresses lymphocyte proliferation. We investigated this immunoregulatory mechanism and find that catalase, an H2O2 inhibitor, also enhances IL-2 production by MNC. The addition of PAO, but only in the presence of either endogenous or exogenous spermidine (a polyamine), decreases IL-2 production; this effect is catalase inhibitable. Pre-incubation with spermidine, but not any of three diamines tested, suppresses PHA-stimulated IL-2 production and this effect requires monocytes. Three PAO inhibitors have an enhancing effect on IL-2 production which is again monocyte dependent. These results suggest that: 1) H2O2 produced by PHA-activated PBMC down-regulates IL-2 production; 2) products of the interaction between PAO and spermidine inhibit IL-2 production and H2O2 is essential but apparently not sufficient to mediate this effect; 3) human PBMC contain PAO activity. This polyamine-PAO-dependent inhibitory mechanism might constitute a feedback loop that limits human T cell proliferation and, consequently, also the immune responses mediated by these cells.
Clinical Immunology Section, Audie L. Murphy Memorial Veterans Hospital, San Antonio, TX.
E
E
Flescher
T L
TL
Bowlin
N
N
Talal
D000328:Adult; D002462:Cell Membrane / Q000187:drug effects; D005260:Female; D006801:Humans; D006861:Hydrogen Peroxide; D007376:Interleukin-2 / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D065108:Ornithine Decarboxylase Inhibitors; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011700:Putrescine / Q000031:analogs & derivatives / Q000494:pharmacology; D013095:Spermidine / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D013601:T-Lymphocytes / Q000187:drug effects; D000097667:Polyamine Oxidase
D006861:Hydrogen Peroxide; D007376:Interleukin-2; D065108:Ornithine Decarboxylase Inhibitors; D000587:Oxidoreductases Acting on CH-NH Group Donors; D011700:Putrescine; D013095:Spermidine; D000097667:Polyamine Oxidase; C044445:MDL 72527